Collagen pp 447-474 | Cite as

Genetic Collagen Diseases: Influence of Collagen Mutations on Structure and Mechanical Behavior

  • R.D. Blank
  • A.L. Boskey


Mutations in type I collagen as well as those in the enzymes involved in the processing of type I collagen and in proteins that associate with type I collagen have significant effects on the structure and mechanical properties of the collagen-containing tissues. Osteogenesis imperfecta, also known as “brittle bone disease” provides an illustration of how site-specific mutations and alterations can affect tissue integrity. Examples of other type I collagen diseases are also discussed.


Osteogenesis Imperfecta COL1A2 Gene Collagen Mutation Osteogenesis Imperfecta Type Dentinogenesis Imperfecta 
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  1. Aubin I, Adams CP, Opsahl S, Septier D, Bishop CE, Auge N, Salvayre R, Negre-Salvayre A, Goldberg M, Guenet JL, Poirier C (2005) A deletion in the gene encoding sphingomyelin phosphodiesterase 3 (Smpd3) results in osteogenesis and dentinogenesis imperfecta in the mouse. Nat Genet. 37:803–805.CrossRefGoogle Scholar
  2. Bachinger HP, Morris NP, Davis JM (1993) Thermal stability and folding of the collagen triple helix and the effects of mutations in osteogenesis imperfecta on the triple helix of type I collagen. Am J Med Genet. 45:152–162.CrossRefGoogle Scholar
  3. Balemans W, Van Hul W (2007) The genetics of low-density lipoprotein receptor-related protein 5 in bone: a story of extremes. Endocrinology.148:2622–2629.CrossRefGoogle Scholar
  4. Balk ML, Bray J, Day C, Epperly M, Greenberger J, Evans CH, Niyibizi C (1997) Effect of\break rhBMP-2 on the osteogenic potential of bone marrow stromal cells from an osteogenesis imperfecta mouse (oim). Bone. 21:7–15.CrossRefGoogle Scholar
  5. Bard JB, Kratochwil K (1987) Corneal morphogenesis in the Mov13 mutant mouse is characterized by normal cellular organization but disordered and thin collagen. Development. 101:547–555.Google Scholar
  6. Barnes AM, Chang W, Morello R, Cabral WA, Weis M, Eyre DR, Leikin S, Makareeva E, Kuznetsova N, Uveges TE, Ashok A, Flor AW, Mulvihill JJ, Wilson PL, Sundaram UT, Lee B, Marini JC (2006) Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta. N Engl J Med. 355:2757–2764.CrossRefGoogle Scholar
  7. Bateman JF, Mascara T, Cole WG, Stacey A, Jaenisch R (1989) Collagen protein abnormalities produced by site-directed mutagenesis of the pro alpha 1(I) gene. Connect Tissue Res. 20:\break 205–212.CrossRefGoogle Scholar
  8. Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ (1998) Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK). Am J Med Genet.77:31–37.CrossRefGoogle Scholar
  9. Bodine PV, Komm BS (2006) Wnt signaling and osteoblastogenesis. Rev Endocr Metab Disord. 7:33–39.CrossRefGoogle Scholar
  10. Bonadio J, Saunders TL, Tsai E, Goldstein SA, Morris-Wiman J, Brinkley L, Dolan DF, Altschuler RA, Hawkins JE, Bateman JF, Mascara T, Jaenisch R (1990) Transgenic mouse model of the mild dominant form of osteogenesis imperfecta. Proc Natl Acad Sci USA. 87: 7145–7149.CrossRefGoogle Scholar
  11. Bonadio J, Jepsen KJ, Mansoura MK, Jaenisch R, Kuhn JL, Goldstein SA (1993) A murine skeletal adaptation that significantly increases cortical bone mechanical properties. Implications for human skeletal fragility. J Clin Invest. 92:1697–1705.Google Scholar
  12. Breindl M, Harbers K, Jaenisch R (1984) Retrovirus-induced lethal mutation in collagen I gene of mice is associated with an altered chromatin structure. Cell. 38:9–16.CrossRefGoogle Scholar
  13. Brenner RE, Vetter U, Stoss H, Muller PK, Teller WM (1993) Defective collagen fibril formation and mineralization in osteogenesis imperfecta with congenital joint contractures (Bruck syndrome). Eur J Pediatr. 152:505–508.CrossRefGoogle Scholar
  14. Bristow J, Carey W, Egging D, Schalkwijk J (2005) Tenascin-X, collagen, elastin, and the Ehlers-Danlos syndrome. Am J Med Genet C Semin Med Genet. 139:24–30.Google Scholar
  15. Byers PH (1993) Osteogenesis Imperfecta in Royce PM and Steinmann B (eds) Connective Tissues and Its Heritable Disorders, Wiley Liss, New York, pp 317–350.Google Scholar
  16. Byers PH, Wallis GA, Willing MC (1991) Osteogenesis imperfecta: translation of mutation to phenotype. J Med Genet. 28:433–442.Google Scholar
  17. Byers PH, Duvic M, Atkinson M, Robinow M, Smith LT, Krane SM, Greally MT, Ludman M, Matalon R, Pauker S, Quanbeck D, Schwarze U (1997) Ehlers-Danlos syndrome type VIIA and VIIB result from splice-junction mutations or genomic deletions that involve exon 6 in the COL1A1 and COL1A2 genes of type I collagen. Am J Med Genet. 72:94–105.CrossRefGoogle Scholar
  18. Cabral WA, Makareeva E, Colige A, Letocha AD, Ty JM, Yeowell HN, Pals G, Leikin S, Marini JC (2005) Mutations near amino end of alpha1(I) collagen cause combined osteogenesis imperfecta/Ehlers-Danlos syndrome by interference with N-propeptide processing. J Biol Chem. 280:19259–19269.CrossRefGoogle Scholar
  19. Cabral WA, Chang W, Barnes AM, Weis M, Scott MA, Leikin S, Makareeva E, Kuznetsova NV, Rosenbaum KN, Tifft CJ, Bulas DI, Kozma C, Smith PA, Eyre DR, Marini JC (2007) Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta. Nat Genet. 39:359–365.CrossRefGoogle Scholar
  20. Camacho NP, Hou L, Toledano TR, Ilg WA, Brayton CF, Raggio CL, Root L, Boskey AL (1999) The material basis for reduced mechanical properties in oim mice bones. J Bone Miner Res. 14:264–272.CrossRefGoogle Scholar
  21. Camacho NP, Raggio CL, Doty SB, Root L, Zraick V, Ilg WA, Toledano TR, Boskey AL (2001) A controlled study of the effects of alendronate in a growing mouse model of osteogenesis imperfecta. Calcif Tissue Int. 69:94–101.CrossRefGoogle Scholar
  22. Campbell BG, Wootton JA, Krook L, DeMarco J, Minor RR (1997) Clinical signs and diagnosis of osteogenesis imperfecta in three dogs. J Am Vet Med Assoc. 211:183–187.Google Scholar
  23. Cassella JP, Barber P, Catterall AC, Ali SY (1994) A morphometric analysis of osteoid collagen fibril diameter in osteogenesis imperfecta. Bone.15:329–334.CrossRefGoogle Scholar
  24. Cheung MS, Glorieux FH, Rauch F (2007) Natural history of hyperplastic callus formation in osteogenesis imperfecta type V. J Bone Miner Res. 22:1181–1186.CrossRefGoogle Scholar
  25. Chiodo AA, Hockey A, Cole WG (1992) A base substitution at the splice acceptor site of intron 5 of the COL1A2 gene activates a cryptic splice site within exon 6 and generates abnormal type I procollagen in a patient with Ehlers-Danlos syndrome type VII. J Biol Chem. 267:6361–6369.Google Scholar
  26. Chipman SD, Sweet HO, McBride DJ Jr, Davisson MT, Marks SC Jr, Shuldiner AR, Wenstrup RJ, Rowe DW, Shapiro JR (1993) Defective pro alpha 2(I) collagen synthesis in a recessive mutation in mice: a model of human osteogenesis imperfecta. Proc Natl Acad Sci USA. 90: 1701–1705.CrossRefGoogle Scholar
  27. Cohen-Solal L, Zolezzi F, Pignatti PF, Mottes M (1996) Intrafamilial variable expressivity of osteogenesis imperfecta due to mosaicism for a lethal G382R substitution in the COL1A1 gene. Mol Cell Probes. 10:219–225.CrossRefGoogle Scholar
  28. Cohn LA, Meuten DJ (1990) Bone fragility in a kitten: an osteogenesis imperfecta-like syndrome. J Am Vet Med Assoc. 197:98–100.Google Scholar
  29. Cole WG, Chan D, Chambers GW, Walker ID, Bateman JF (1986) Deletion of 24 amino acids from the pro-alpha 1(I) chain of type I procollagen in a patient with the Ehlers-Danlos syndrome type VII. J Biol Chem. 261:5496–5503.Google Scholar
  30. Constantinou CD, Pack M, Young SB, Prockop DJ (1990) Phenotypic heterogeneity in osteogenesis imperfecta: the mildly affected mother of a proband with a lethal variant has the same mutation substituting cysteine for alpha 1-glycine 904 in a type I procollagen gene (COL1A1). Am J Hum Genet. 47:670–679.Google Scholar
  31. Constantinou-Deltas CD, Ladda RL, Prockop DJ (1993) Somatic cell mosaicism: another source of phenotypic heterogeneity in nuclear families with osteogenesis imperfecta. Am J Med Genet 45:246–251.CrossRefGoogle Scholar
  32. Czarny-Ratajczak M, Lohiniva J, Rogala P, Kozlowski K, Perala M, Carter L, Spector TD, Kolodziej L, Seppanen U, Glazar R, Krolewski J, Latos-Bielenska A, Ala-Kokko L (2001) A mutation in COL9A1 causes multiple epiphyseal dysplasia: further evidence for locus heterogeneity. Am J Hum Genet. 69:969–980.CrossRefGoogle Scholar
  33. D’Alessio M, Ramirez F, Blumberg BD, Wirtz MK, Rao VH, Godfrey MD, Hollister DW (1991) Characterization of a COL1A1 splicing defect in a case of Ehlers-Danlos syndrome type VII: further evidence of molecular homogeneity. Am J Hum Genet 49:400–406.Google Scholar
  34. Dalgleish R (1997) The human type I collagen mutation database. Nucleic Acids Res. 25:181–187.CrossRefGoogle Scholar
  35. Dalgleish R (1998) The human collagen mutation database 1998. Nucleic Acids Res. 26:253–255.CrossRefGoogle Scholar
  36. Dawson PA, Kelly TE, Marini JC (1999) Extension of phenotype associated with structural mutations in type I collagen: siblings with juvenile osteoporosis have an alpha2(I)Gly436 ⟶ Arg substitution. J Bone Miner Res. 14:449–455.CrossRefGoogle Scholar
  37. Deak SB, Nicholls A, Pope FM, Prockop DJ (1983). The molecular defect in a nonlethal variant of osteogenesis imperfecta. Synthesis of pro-alpha 2(I) chains which are not incorporated into trimers of type I procollagen. J Biol Chem. 258:15192–15197.Google Scholar
  38. De Paepe A, Nuytinck L, Raes M, Fryns JP (1997) Homozygosity by descent for a COL1A2 mutation in two sibs with severe osteogenesis imperfecta and mild clinical expression in the heterozygotes. Hum Genet 99:478–483.CrossRefGoogle Scholar
  39. Di Lullo GA, Sweeney SM, Korkko J, Ala-Kokko L, San Antonio JD (2002) Mapping the ligand-binding sites and disease-associated mutations on the most abundant protein in the human, type I collagen. J Biol Chem. 277:4223–4231.CrossRefGoogle Scholar
  40. Edwards MJ, Wenstrup RJ, Byers PH, Cohn DH (1992) Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a mutation in the COL1A2 gene of type I collagen. The mosaic parent exhibits phenotypic features of a mild form of the disease. Hum Mutat. 1:47–54.CrossRefGoogle Scholar
  41. Ee HL, Liu L, Goh CL, McGrath JA (2007) Clinical and molecular dilemmas in the diagnosis of familial epidermolysis bullosa pruriginosa. J Am Acad Dermatol. 56:S77–81.CrossRefGoogle Scholar
  42. Evans KD, Lau ST, Oberbauer AM, Martin RB (2003) Alendronate affects long bone length and growth plate morphology in the oim mouse model for Osteogenesis Imperfecta. Bone. 32: 268–274.CrossRefGoogle Scholar
  43. Evason MD, Taylor SM, Bebchuk TN (2007) Suspect osteogenesis imperfecta in a male kitten. Can Vet J. 48:296–298.Google Scholar
  44. Eyre DR, Shapiro FD, Aldridge JF (1985) A heterozygous collagen defect in a variant of the Ehlers-Danlos syndrome type VII. Evidence for a deleted amino-telopeptide domain in the pro-alpha 2(I) chain. J Biol Chem. 260:11322–11329.Google Scholar
  45. Feshchenko S, Brinckmann J, Lehmann HW, Koch HG, Muller PK, Kugler S (1998) Identification of a new heterozygous point mutation in the COL1A2 gene leading to skipping of exon 9 in a patient with joint laxity, hyperextensibility of skin and blue sclerae. Mutations in brief no. 166. Online. Hum Mutat. 12:138.Google Scholar
  46. Fichard A, Chanut-Delalande H, Ruggiero F (2003) [The Ehlers-Danlos syndrome: the extracellular matrix scaffold in question] Med Sci (Paris). 19:443–452.Google Scholar
  47. Forlino A, Porter FD, Lee EJ, Westphal H, Marini JC (1999) Use of the Cre/lox recombination system to develop a non-lethal knock-in murine model for osteogenesis imperfecta with an alpha1(I) G349C substitution. Variability in phenotype in BrtlIV mice. J Biol Chem. 274:37923–37931.CrossRefGoogle Scholar
  48. Forlino A, Tani C, Rossi A, Lupi A, Campari E, Gualeni B, Bianchi L, Armini A, Cetta G, Bini L, Marini JC (2007) Differential expression of both extracellular and intracellular proteins is involved in the lethal or nonlethal phenotypic variation of BrtlIV, a murine model for osteogenesis imperfecta. Proteomics. 7:1877–1891.CrossRefGoogle Scholar
  49. Francis MJ, Williams KJ, Sykes BC, Smith R (1981) The relative amounts of the collagen chains alpha 1(I), alpha 2 and alpha 1(III) in the skin of 31 patients with osteogenesis imperfecta. Clin Sci (Lond). 60:617–623.Google Scholar
  50. Gensure RC, Makitie O, Barclay C, Chan C, Depalma SR, Bastepe M, Abuzahra H, Couper R, Mundlos S, Sillence D, Ala Kokko L, Seidman JG, Cole WG, Juppner H (2005) A novel COL1A1 mutation in infantile cortical hyperostosis (Caffey disease) expands the spectrum of collagen-related disorders. J Clin Invest. 115:1250–1257.Google Scholar
  51. Giunta C, Superti-Furga A, Spranger S, Cole WG, Steinmann B (1999) Ehlers-Danlos syndrome type VII: clinical features and molecular defects. J Bone Joint Surg Am. 81: 225–238.Google Scholar
  52. Glorieux FH, Rauch F, Plotkin H, Ward L, Travers R, Roughley P, Lalic L, Glorieux DF, Fassier F, Bishop NJ (2000) Type V osteogenesis imperfecta: a new form of brittle bone disease. J Bone Miner Res. 15:1650–1658.CrossRefGoogle Scholar
  53. Glorieux FH, Ward LM, Rauch F, Lalic L, Roughley PJ, Travers R (2002) Osteogenesis imperfecta type VI: a form of brittle bone disease with a mineralization defect. J Bone Miner Res. 17: 30–38.CrossRefGoogle Scholar
  54. Gong Y, Vikkula M, Boon L, Liu J, Beighton P, Ramesar R, Peltonen L, Somer H, Hirose T, Dallapiccola B, De Paepe A, Swoboda W, Zabel B, Superti-Furga A, Steinmann B, Brunner HG, Jans A, Boles RG, Adkins W, van den Boogaard MJ, Olsen BR, Warman ML (1996). Osteoporosis-pseudoglioma syndrome, a disorder affecting skeletal strength and vision, is assigned to chromosome region 11q12–13. Am J Hum Genet. 59:146–151.Google Scholar
  55. Grabner B, Landis WJ, Roschger P, Rinnerthaler S, Peterlik H, Klaushofer K, Fratzl P (2001) Age- and genotype-dependence of bone material properties in the osteogenesis imperfecta murine model (oim). Bone. 29:453–457.CrossRefGoogle Scholar
  56. Harbers K, Kuehn M, Delius H, Jaenisch R (1984) Insertion of retrovirus into the first intron of alpha 1(I) collagen gene to embryonic lethal mutation in mice. Proc Natl Acad Sci USA 81:1504–1508.CrossRefGoogle Scholar
  57. Hartung S, Jaenisch R, Breindl M (1986) Retrovirus insertion inactivates mouse alpha 1(I) collagen gene by blocking initiation of transcription. Nature. 320:365–367.CrossRefGoogle Scholar
  58. Hata R, Kurata S, Shinkai H (1988) Existence of malfunctioning pro alpha2(I) collagen genes in a patient with a pro alpha 2(I)-chain-defective variant of Ehlers-Danlos syndrome. Eur J Biochem. 174:231–237.CrossRefGoogle Scholar
  59. Ha-Vinh R, Alanay Y, Bank RA, Campos-Xavier AB, Zankl A, Superti-Furga A, Bonafe L (2004) Phenotypic and molecular characterization of Bruck syndrome (osteogenesis imperfecta with contractures of the large joints) caused by a recessive mutation in PLOD2. Am J Med Genet A.131:115–120.CrossRefGoogle Scholar
  60. Ho KK, Kong RY, Kuffner T, Hsu LH, Ma L, Cheah KS (1994) Further evidence that the failure to cleave the aminopropeptide of type I procollagen is the cause of Ehlers-Danlos syndrome type VII. Hum Mutat. 3:358–364.CrossRefGoogle Scholar
  61. Hermanns-Le T, Pierard GE (2006) Collagen fibril arabesques in connective tissue disorders. Am J Clin Dermatol. 7:323–326.CrossRefGoogle Scholar
  62. Houdebine LM (2002) The methods to generate transgenic animals and to control transgene expression. J Biotechnol. 98:145–160.CrossRefGoogle Scholar
  63. Hyde TJ, Bryan MA, Brodsky B, Baum J (2006) Sequence dependence of renucleation after a Gly mutation in model collagen peptides. J Biol Chem. 281:36937–36943.CrossRefGoogle Scholar
  64. Jaenisch R, Harbers K, Schnieke A, Lohler J, Chumakov I, Jahner D, Grotkopp D, Hoffmann E (1983) Germline integration of moloney murine leukemia virus at the Mov13 locus leads to recessive lethal mutation and early embryonic death. Cell. 32:209–216.CrossRefGoogle Scholar
  65. Jahner D, Jaenisch R (1985) Retrovirus-induced de novo methylation of flanking host sequences correlates with gene inactivity. Nature. 315:594–597.CrossRefGoogle Scholar
  66. Jenkins CL, Bretscher LE, Guzei IA, Raines RT (2003) Effect of 3-hydroxyproline residues on collagen stability. J Am Chem Soc. 125:6422–6427.CrossRefGoogle Scholar
  67. Jensen PT, Rasmussen PG, Basse A (1976) Congenital osteogenesis imperfecta in Charollais cattle. Nord Vet Med. 28:304–308.Google Scholar
  68. Jepsen KJ, Goldstein SA, Kuhn JL, Schaffler MB, Bonadio J (1996). Type-I collagen mutation compromises the post-yield behavior of Mov13 long bone. J Orthop Res. 14:493–499.Google Scholar
  69. Jepsen KJ, Schaffler MB, Kuhn JL, Goulet RW, Bonadio J, Goldstein SA (1997). Type I collagen mutation alters the strength and fatigue behavior of Mov13 cortical tissue. J Biomech. 30: 1141–1147.CrossRefGoogle Scholar
  70. Kamoun-Goldrat AS, Le Merrer MF (2007) Animal models of osteogenesis imperfecta and related syndromes. J Bone Miner Metab. 25:211–218.CrossRefGoogle Scholar
  71. Kato M, Patel MS, Levasseur R, Lobov I, Chang BH, Glass DA 2nd, Hartmann C, Li L, Hwang TH, Brayton CF, Lang RA, Karsenty G, Chan L (2002) Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol. 157:303–314.CrossRefGoogle Scholar
  72. Kefalides NA (1973) Structure and biosynthesis of basement membranes. Int Rev Connect Tissue Res. 6:63–104.Google Scholar
  73. Khillan JS, Olsen AS, Kontusaari S, Sokolov B, Prockop DJ (1991) Transgenic mice that express a mini-gene version of the human gene for type I procollagen (COL1A1) develop a phenotype resembling a lethal form of osteogenesis imperfecta. J Biol Chem. 266:23373–23379.Google Scholar
  74. King D, Chase J, Havey RM, Voronov L, Sartori M, McEwen HA, Beamer WG, Patwardhan AG (2005a) Effects of growth hormone transgene expression on vertebrae in a mouse model of osteogenesis imperfecta. Spine. 30:1491–1495.Google Scholar
  75. King D, Jarjoura D, McEwen HA, Askew MJ (2005b) Growth hormone injections improve bone quality in a mouse model of osteogenesis imperfecta. J Bone Miner Res. 20:987–993.Google Scholar
  76. Kozloff KM, Carden A, Bergwitz C, Forlino A, Uveges TE, Morris MD, Marini JC, Goldstein SA (2004) Brittle IV mouse model for osteogenesis imperfecta IV demonstrates postpubertal adaptations to improve whole bone strength. J Bone Miner Res. 19:614–622.CrossRefGoogle Scholar
  77. Kratochwil K, Dziadek M, Lohler J, Harbers K, Jaenisch R (1986) Normal epithelial branching morphogenesis in the absence of collagen I. Dev Biol. 117:596–606.CrossRefGoogle Scholar
  78. Kratochwil K, von der Mark K, Kollar EJ, Jaenisch R, Mooslehner K, Schwarz M, Haase K, Gmachl I, Harbers K (1989) Retrovirus-induced insertional mutation in Mov13 mice affects collagen I expression in a tissue-specific manner. Cell. 57:807–816.CrossRefGoogle Scholar
  79. Kuivaniemi H, Tromp G, Prockop DJ (1997) Mutations in fibrillar collagens (types I, II, III, and XI), fibril-associated collagen (type IX), and network-forming collagen (type X) cause a spectrum of diseases of bone, cartilage, and blood vessels. Hum Mutat. 9:300–315.CrossRefGoogle Scholar
  80. Kuznetsova NV, McBride DJ, Leikin S (2003) Changes in thermal stability and microunfolding pattern of collagen helix resulting from the loss of alpha2(I) chain in osteogenesis imperfecta murine. J Mol Biol. 331:191–200.CrossRefGoogle Scholar
  81. Kuznetsova NV, Forlino A, Cabral WA, Marini JC, Leikin S (2004) Structure, stability and interactions of type I collagen with GLY349-CYS substitution in alpha 1(I) chain in a murine Osteogenesis Imperfecta model. Matrix Biol. 23:101–112.CrossRefGoogle Scholar
  82. Lehmann HW, Mundlos S, Winterpacht A, Brenner RE, Zabel B, Muller PK (1994) Ehlers-Danlos syndrome type VII: phenotype and genotype. Arch Dermatol Res. 286:425–428.CrossRefGoogle Scholar
  83. Lethias C, Carisey A, Comte J, Cluzel C, Exposito JY (2006) A model of tenascin-X integration within the collagenous network. FEBS Lett. 580:6281–6285.CrossRefGoogle Scholar
  84. Lohler J, Timpl R, Jaenisch R (1984) Embryonic lethal mutation in mouse collagen I gene causes rupture of blood vessels and is associated with erythropoietic and mesenchymal cell death. Cell. 38:597–607.CrossRefGoogle Scholar
  85. Lopez Franco GE, Huang A, Pleshko Camacho N, Blank RD (2005) Dental phenotype of the col1a2(oim) mutation: DI is present in both homozygotes and heterozygotes. Bone. 36: 1039–1046.CrossRefGoogle Scholar
  86. Lopez Franco GE, Huang A, Pleshko Camacho N, Stone DS, Blank RD (2006). Increased Young’s modulus and hardness of Col1a2 oim dentin. J Dent Res. 85:1032–1036.Google Scholar
  87. Makareeva E, Cabral WA, Marini JC, Leikin S (2006) Molecular mechanism of alpha 1(I)-osteogenesis imperfecta/Ehlers-Danlos syndrome: unfolding of an N-anchor domain at the N-terminal end of the type I collagen triple helix. J Biol Chem. 281:6463–6470.CrossRefGoogle Scholar
  88. Malfait F, De Paepe A (2005) Molecular genetics in classic Ehlers-Danlos syndrome. Am J Med Genet C Semin Med Genet. 139:17–23.Google Scholar
  89. Malfait F, Symoens S, Coucke P, Nunes L, De Almeida S, De Paepe A (2006) Total absence of the alpha2(I) chain of collagen type I causes a rare form of Ehlers-Danlos syndrome with hypermobility and propensity to cardiac valvular problems. J Med Genet. 43:e36.CrossRefGoogle Scholar
  90. Malfait F, Symoens S, De Backer J, Hermanns-Le T, Sakalihasan N, Lapiere CM, Coucke P, De Paepe A (2007) Three arginine to cysteine substitutions in the pro-alpha (I)-collagen chain cause Ehlers-Danlos syndrome with a propensity to arterial rupture in early adulthood. Hum Mutat. 28:387–395.CrossRefGoogle Scholar
  91. Marini JC (2006) Osteogenesis Imperfecta. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. M. J. Favus. Washington, DC., American Society for Bone and Mineral Research:418–420.Google Scholar
  92. Marini JC, Cabral WA, Barnes AM, Chang W (2007a) Components of the collagen prolyl 3-hydroxylation complex are crucial for normal bone development. Cell Cycle. 6:1675–1681.Google Scholar
  93. Marini JC, Forlino A, Cabral WA, Barnes AM, San Antonio JD, Milgrom S, Hyland JC, Korkko J, Prockop DJ, De Paepe A, Coucke P, Symoens S, Glorieux FH, Roughley PJ, Lund AM, Kuurila-Svahn K, Hartikka H, Cohn DH, Krakow D, Mottes M, Schwarze U, Chen D, Yang K, Kuslich C, Troendle J, Dalgleish R, Byers PH (2007b). Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans. Hum Mutat. 28:209–221.Google Scholar
  94. Masunaga T (2006) Epidermal basement membrane: its molecular organization and blistering disorders. Connect Tissue Res. 47:55–66.CrossRefGoogle Scholar
  95. Mayer SA, Rubin BS, Starman BJ, Byers PH (1996) Spontaneous multivessel cervical artery dissection in a patient with a substitution of alanine for glycine (G13A) in the alpha 1 (I) chain of type I collagen. Neurology. 47:552–556.Google Scholar
  96. McBride DJ Jr, Choe V, Shapiro JR, Brodsky B (1997) Altered collagen structure in mouse tail tendon lacking the alpha 2(I) chain. J Mol Biol. 270:275–284.CrossRefGoogle Scholar
  97. McCarthy EA, Raggio CL, Hossack MD, Miller EA, Jain S, Boskey AL, Camacho NP (2002) Alendronate treatment for infants with osteogenesis imperfecta: demonstration of efficacy in a mouse model. Pediatr Res. 52:660–670.Google Scholar
  98. Miller E, Delos D, Baldini T, Wright TM, Camacho NP (2007) Abnormal mineral-matrix interactions are a significant contributor to fragility in oim/oim bone. Calcif Tissue Int. 81:206–214.CrossRefGoogle Scholar
  99. Misof K, Landis WJ, Klaushofer K, Fratzl P (1997) Collagen from the osteogenesis imperfecta mouse model (oim) shows reduced resistance against tensile stress. J Clin Invest. 100:40–45.CrossRefGoogle Scholar
  100. Mizuno K, Hayashi T, Peyton DH, Bachinger HP (2004) The peptides acetyl-(Gly-3(S)Hyp-4(R)Hyp)10-NH2 and acetyl-(Gly-Pro-3(S)Hyp)10-NH2 do not form a collagen triple helix. J Biol Chem. 279:282–287.CrossRefGoogle Scholar
  101. Morello R., Bertin TK, Chen Y, Hicks J, Tonachini L, Monticone M, Castagnola P, Rauch F, Glorieux FH, Vranka J, Bächinger HP, Pace JM, Schwarze U, Byersn PH, Weis M, Fernandes RJ, Eyre DR, Yao Z, Boyce BF, Lee B (2006) CRTAP is required for prolyl 3- hydroxylation and mutations cause recessive osteogenesis imperfecta. Cell. 127:291–304.CrossRefGoogle Scholar
  102. Morike M, Brenner RE, Bushart GB, Teller WM, Vetter U (1992) Collagen metabolism in cultured osteoblasts from osteogenesis imperfecta patients. Biochem J. 286(Pt 1):73–77.Google Scholar
  103. Mottes M, Sangalli A, Valli M, Gomez Lira M, Tenni R, Buttitta P, Pignatti PF, Cetta G (1992) Mild dominant osteogenesis imperfecta with intrafamilial variability: the cause is a serine for glycine alpha 1(I) 901 substitution in a type- I collagen gene. Hum Genet. 89:480–484.CrossRefGoogle Scholar
  104. Mottes M, Gomez Lira MM, Valli M, Scarano G, Lonardo F, Forlino A, Cetta G, Pignatti PF (1993) Paternal mosaicism for a COL1A1 dominant mutation (alpha 1 Ser-415) causes recurrent osteogenesis imperfecta. Hum Mutat. 2:196–204.CrossRefGoogle Scholar
  105. Muriel MP, Bonaventure J, Stanescu R, Maroteaux P, Guenet JL, Stanescu V (1991) Morphological and biochemical studies of a mouse mutant (fro/fro) with bone fragility. Bone. 12:241–248.CrossRefGoogle Scholar
  106. Myllyla R, Wang C, Heikkinen J, Juffer A, Lampela O, Risteli M, Ruotsalainen H, Salo A, Sipila L (2007) Expanding the lysyl hydroxylase toolbox: new insights into the localization and activities of lysyl hydroxylase 3 (LH3). J Cell Physiol. 212:323–329.CrossRefGoogle Scholar
  107. Nicholls AC, Oliver J, Renouf DV, McPheat J, Palan A, Pope FM (1991) Ehlers-Danlos syndrome type VII: a single base change that causes exon skipping in the type I collagen alpha 2(I) chain. Hum Genet. 87:193–198.Google Scholar
  108. Nicholls AC, Oliver J, Renouf DV, Heath DA, Pope FM (1992) The molecular defect in a family with mild atypical osteogenesis imperfecta and extreme joint hypermobility: exon skipping caused by an 11-bp deletion from an intron in one COL1A2 allele. Hum Genet. 88:627–633.CrossRefGoogle Scholar
  109. Nicholls AC, Oliver J, McCarron S, Winter GB, Pope FM (1996) Splice site mutation causing deletion of exon 21 sequences from the pro alpha 2(I) chain of type I collagen in a patient with severe dentinogenesis imperfecta but very mild osteogenesis imperfecta. Hum Mutat. 7: 219–227.CrossRefGoogle Scholar
  110. Nicholls AC, Sher JL, Wright MJ, Oley C, Mueller RF, Pope FM (2000) Clinical phenotypes and molecular characterisation of three patients with Ehlers-Danlos syndrome type VII. J Med Genet. 37:E33.CrossRefGoogle Scholar
  111. Nicholls AC, Valler D, Wallis S, Pope FM (2001) Homozygosity for a splice site mutation of the COL1A2 gene yields a non-functional pro(alpha)2(I) chain and an EDS/OI clinical phenotype. J Med Genet. 38:132–136.CrossRefGoogle Scholar
  112. Niyibizi C, Smith P, Mi Z, Phillips CL, Robbins P (2001) Transfer of proalpha2(I) cDNA into cells of a murine model of human Osteogenesis Imperfecta restores synthesis of type I collagen comprised of alpha1(I) and alpha2(I) heterotrimers in vitro and in vivo. J Cell Biochem. 83: 84–91.CrossRefGoogle Scholar
  113. Nuytinck L, Freund M, Lagae L, Pierard GE, Hermanns-Le T, De Paepe A (2000) Classical Ehlers-Danlos syndrome caused by a mutation in type I collagen. Am J Hum Genet. 66:1398–1402.Google Scholar
  114. Otterbach B, Stoffel W (1995) Acid sphingomyelinase-deficient mice mimic the neurovisceral form of human lysosomal storage disease (Niemann-Pick disease). Cell. 81:1053–1061.CrossRefGoogle Scholar
  115. Oyama M, Tatlock A, Fukuta S, Kavalkovich K, Nishimura K, Johnstone B, Robbins PD, Evans CH, Niyibizi C (1999) Retrovirally transduced bone marrow stromal cells isolated from a mouse model of human osteogenesis imperfecta (oim) persist in bone and retain the ability to form cartilage and bone after extended passaging. Gene Ther. 6:321–329.CrossRefGoogle Scholar
  116. Paterson CR, Mole PA (1994) Bone density in osteogenesis imperfecta may well be normal [see comments]. Postgrad Med J. 70:104–107.Google Scholar
  117. Peltonen L, Palotie A, Prockop DJ (1980) A defect in the structure of type I procollagen in a patient who had osteogenesis imperfecta: excess mannose in the COOH-terminal propeptide. Proc Natl Acad Sci USA. 77:6179–6183.CrossRefGoogle Scholar
  118. Pereira R, Khillan JS, Helminen HJ, Hume EL, Prockop DJ (1993) Transgenic mice expressing a partially deleted gene for type I procollagen (COL1A1). A breeding line with a phenotype of spontaneous fractures and decreased bone collagen and mineral. J Clin Invest. 91: 709–716.CrossRefGoogle Scholar
  119. Pereira RF, Hume EL, Halford KW, Prockop DJ (1995) Bone fragility in transgenic mice expressing a mutated gene for type I procollagen (COL1A1) parallels the age-dependent phenotype of human osteogenesis imperfecta. J Bone Miner Res. 10:1837–1843.CrossRefGoogle Scholar
  120. Pfeiffer BJ, Franklin CL, Hsieh FH, Bank RA, Phillips CL (2005) Alpha 2(I) collagen deficient oim mice have altered biomechanical integrity, collagen content, and collagen crosslinking of their thoracic aorta. Matrix Biol. 24:451–458.CrossRefGoogle Scholar
  121. Phillips CL, Shrago-Howe AW, Pinnell SR, Wenstrup RJ (1990) A substitution at a non-glycine position in the triple-helical domain of pro alpha 2(I) collagen chains present in an individual with a variant of the Marfan syndrome. J Clin Invest 86:1723–1728.CrossRefGoogle Scholar
  122. Phillips CL, Pfeiffer BJ, Luger AM, Franklin CL (2002) Novel collagen glomerulopathy in a homotrimeric type I collagen mouse (oim). Kidney Int. 62:383–391.CrossRefGoogle Scholar
  123. Pollitt R, McMahon R, Nunn J, Bamford R, Afifi A, Bishop N, Dalton A (2006) Mutation analysis of COL1A1 and COL1A2 in patients diagnosed with osteogenesis imperfecta type I–IV. Hum Mutat. 27:716.Google Scholar
  124. Pornprasertsuk S, Duarte WR, Mochida Y, Yamauchi M (2005) Overexpression of lysyl hydroxylase-2b leads to defective collagen fibrillogenesis and matrix mineralization. J Bone Miner Res. 20:81–87.CrossRefGoogle Scholar
  125. Primorac D, Rowe DW, Mottes M, Barisic I, Anticevic D, Mirandola S, Gomez Lira M, Kalajzic I, Kusec V, Glorieux FH (2001) Osteogenesis imperfecta at the beginning of bone and joint decade. Croat Med J. 42:393–415.Google Scholar
  126. Prockop DJ (1984) Osteogenesis imperfecta: phenotypic heterogeneity, protein suicide, short and long collagen. Am J Hum Genet. 36:499–505.Google Scholar
  127. Raff ML, Craigen WJ, Smith LT, Keene DR, Byers PH (2000) Partial COL1A2 gene duplication produces features of osteogenesis imperfecta and Ehlers-Danlos syndrome type VII. Hum Genet. 106:19–28.CrossRefGoogle Scholar
  128. Ristevski S (2005) Making better transgenic models: conditional, temporal, and spatial approaches. Mol Biotechnol. 29:153–163.CrossRefGoogle Scholar
  129. Rowe DW, Shapiro JR, Poirier M, Schlesinger S (1985) Diminished type I collagen synthesis and reduced alpha 1(I) collagen messenger RNA in cultured fibroblasts from patients with dominantly inherited (type I) osteogenesis imperfecta. J Clin Invest. 76:604–611.CrossRefGoogle Scholar
  130. Sarafova, AP, Choi H, Forlino A, Gajko A, Cabral WA, Tosi L, Reing CM, Marini JC (1998) Three novel type I collagen mutations in osteogenesis imperfecta type IV probands are associated with discrepancies between electrophoretic migration of osteoblast and fibroblast collagen. Hum Mutat. 11:395–403.Google Scholar
  131. Sarathchandra P, Pope FM, Kayser MV, Ali SY (2000) A light and electron microscopic study of osteogenesis imperfecta bone samples, with reference to collagen chemistry and clinical phenotype. J Pathol. 192:385–395.CrossRefGoogle Scholar
  132. Schnieke A, Harbers K, Jaenisch R (1983) Embryonic lethal mutation in mice induced by retrovirus insertion into the alpha 1(I) collagen gene. Nature. 304:315–320.CrossRefGoogle Scholar
  133. Schwarz M, Harbers K, Kratochwil K (1990) Transcription of a mutant collagen I gene is a cell type and stage-specific marker for odontoblast and osteoblast differentiation. Development. 108:717–726.Google Scholar
  134. Schwarze U, Hata R, McKusick VA, Shinkai H, Hoyme HE, Pyeritz RE, Byers PH (2004) Rare autosomal recessive cardiac valvular form of Ehlers-Danlos syndrome results from mutations in the COL1A2 gene that activate the nonsense-mediated RNA decay pathway. Am J Hum Genet. 74:917–930.CrossRefGoogle Scholar
  135. Seidler DG, Faiyaz-Ul-Haque M, Hansen U, Yip GW, Zaidi SH, Teebi AS, Kiesel L, Gottte M (2006) Defective glycosylation of decorin and biglycan, altered collagen structure, and abnormal phenotype of the skin fibroblasts of an Ehlers-Danlos syndrome patient carrying the novel Arg270Cys substitution in galactosyltransferase I (beta4GalT-7). J Mol Med. 84: 583–594.CrossRefGoogle Scholar
  136. Shapiro JR, Burn VE, Chipman SD, Velis KP, Bansal M (1989) Osteoporosis and familial idiopathic scoliosis: association with an abnormal alpha 2(I) collagen. Connect Tissue Res. 21: 117–123.CrossRefGoogle Scholar
  137. Shapiro JR, Stover ML, Burn VE, McKinstry MB, Burshell AL, Chipman SD, Rowe DW (1992) An osteopenic nonfracture syndrome with features of mild osteogenesis imperfecta associated with the substitution of a cysteine for glycine at triple helix position 43 in the pro alpha 1(I) chain of type I collagen. J Clin Invest 89:567–573.CrossRefGoogle Scholar
  138. Sillence DO, Senn A, Danks DM (1979) Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. 16:101–116.CrossRefGoogle Scholar
  139. Sillence DO, Ritchie HE, Dibbayawan T, Eteson D, Brown K (1993). Fragilitas ossium (fro/fro) in the mouse: a model for a recessively inherited type of osteogenesis imperfecta. Am J Med Genet. 45:276–283.CrossRefGoogle Scholar
  140. Slayton RL, Deschenes SP, Willing MC (2000) Nonsense mutations in the COL1A1 gene preferentially reduce nuclear levels of mRNA but not hnRNA in osteogenesis imperfecta type I cell strains. Matrix Biol. 19:1–9.CrossRefGoogle Scholar
  141. Spotila LD, Constantinou CD, Sereda L, Ganguly A, Riggs BL, Prockop DJ (1991) Mutation in a gene for type I procollagen (COL1A2) in a woman with postmenopausal osteoporosis: evidence for phenotypic and genotypic overlap with mild osteogenesis imperfecta. Proc Natl Acad Sci USA. 88:5423–5427.CrossRefGoogle Scholar
  142. Spotila LD, Colige A, Sereda L, Constantinou-Deltas CD, Whyte MP, Riggs BL, Shaker JL, Spector TD, Hume E, Olsen N, et al. (1994) Mutation analysis of coding sequences for type I procollagen in individuals with low bone density. J Bone Miner Res. 9:923–932.Google Scholar
  143. Stacey A, Bateman J, Choi T, Mascara T, Cole W, Jaenisch R (1988) Perinatal lethal osteogenesis imperfecta in transgenic mice bearing an engineered mutant pro-alpha 1(I) collagen gene. Nature. 332:131–136.CrossRefGoogle Scholar
  144. Stankovic KM, Kristiansen AG, Bizaki A, Lister M, Adams JC, McKenna MJ (2007) Studies of otic capsule morphology and gene expression in the Mov13 mouse – an animal model of type I osteogenesis imperfecta. Audiol Neurootol. 12:334–343.CrossRefGoogle Scholar
  145. Steinmann B, Tuderman L, Peltonen L, Martin GR, McKusick VA, Prockop DJ (1980) Evidence for a structural mutation of procollagen type I in a patient with the Ehlers-Danlos syndrome type VII. J Biol Chem. 255:8887–8893.Google Scholar
  146. Stoffel W, Jenke B, Block B, Zumbansen M, Koebke J (2005) Neutral sphingomyelinase 2 (smpd3) in the control of postnatal growth and development. Proc Natl Acad Sci USA. 102: 4554–4559.CrossRefGoogle Scholar
  147. Stoffel W, Jenke B, Holz B, Binczek E, Gunter RH, Knifka J, Koebke J, Niehoff A (2007) Neutral sphingomyelinase (SMPD3) deficiency causes a novel form of chondrodysplasia and dwarfism that is rescued by Col2A1-driven smpd3 transgene expression. Am J Pathol. 171: 153–161.CrossRefGoogle Scholar
  148. Superti-Furga A, Pistone F, Romano C, Steinmann B (1989) Clinical variability of osteogenesis imperfecta linked to COL1A2 and associated with a structural defect in the type I collagen molecule. J Med Genet. 26:358–362.Google Scholar
  149. Suphapeetiporn K, Tongkobpetch S, Mahayosnond A, Shotelersuk V (2007) Expanding the phenotypic spectrum of Caffey disease. Clin Genet. 71:280–284.CrossRefGoogle Scholar
  150. Sykes B, Francis MJ, Smith R (1977) Altered relation of two collagen types in osteogenesis imperfecta. N Engl J Med. 296:1200–1203.Google Scholar
  151. Symoens S, Nuytinck L, Legius E, Malfait F, Coucke PJ, De Paepe A (2004) Met> Val substitution in a highly conserved region of the pro-alpha1(I) collagen C-propeptide domain causes alternative splicing and a mild EDS/OI phenotype. J Med Genet. 41:e96.CrossRefGoogle Scholar
  152. Tenni R, Biglino P, Dyne K, Rossi A, Filocamo M, Pendola F, Brunelli P, Buttitta P, Borrone C, Cetta G (1991) Phenotypic variability and abnormal type I collagen unstable at body temperature in a family with mild dominant osteogenesis imperfecta. J Inherit Metab Dis. 14:189–201.CrossRefGoogle Scholar
  153. Thorner PS (2007) Alport syndrome and thin basement membrane nephropathy. Nephron Clin Pract. 106:c82–c88.CrossRefGoogle Scholar
  154. Tkocz C, Kuhn K (1969) The formation of triple-helical collagen molecules from alpha-1 or alpha-2 polypeptide chains. Eur J Biochem. 7:454–462.CrossRefGoogle Scholar
  155. Van Camp G, Snoeckx RL, Hilgert N, van den Ende J, Fukuoka H, Wagatsuma M, Suzuki H, Smets RM, Vanhoenacker F, Declau F, Van de Heyning P, Usami S. (2006) A new autosomal recessive form of Stickler syndrome is caused by a mutation in the COL9A1 gene. Am J Hum Genet. 79:449–457.CrossRefGoogle Scholar
  156. Vasan NS, Kuivaniemi H, Vogel BE, Minor RR, Wootton JA, Tromp G, Weksberg R, Prockop DJ (1991) A mutation in the pro alpha 2(I) gene (COL1A2) for type I procollagen in Ehlers-Danlos syndrome type VII: evidence suggesting that skipping of exon 6 in RNA splicing may be a common cause of the phenotype. Am J Hum Genet 48:305–317.Google Scholar
  157. Vranka JA, Sakai LY, Bachinger HP (2004) Prolyl 3-hydroxylase 1, enzyme characterization and identification of a novel family of enzymes. J Biol Chem. 279:23615–23621.CrossRefGoogle Scholar
  158. Wallis GA, Starman BJ, Zinn AB, Byers PH (1990) Variable expression of osteogenesis imperfecta in a nuclear family is explained by somatic mosaicism for a lethal point mutation in the alpha 1(I) gene (COL1A1) of type I collagen in a parent. Am J Hum Genet. 46:1034–1040.Google Scholar
  159. Walter K, Tansek M, Tobias ES, Ikegawa S, Coucke P, Hyland J, Mortier G, Iwaya T, Nishimura G, Superti-Furga A, Unger S (2007) COL2A1-related skeletal dysplasias with predominant metaphyseal involvement. Am J Med Genet A. 143:161–167.Google Scholar
  160. Wang XM, Cui FZ, Ge J, Zhang Y, Ma C (2002) Variation of nanomechanical properties of bone by gene mutation in the zebrafish. Biomaterials. 23:4557–4563.CrossRefGoogle Scholar
  161. Wang XM, Cui FZ, Ge J, Wang Y (2004) Hierarchical structural comparisons of bones from wild-type and liliput (dtc232) gene-mutated Zebrafish. J Struct Biol. 14:236–245.CrossRefGoogle Scholar
  162. Ward LM, Rauch F, Travers R, Chabot G, Azouz EM, Lalic L, Roughley PJ, Glorieux FH (2002) Osteogenesis imperfecta type VII: an autosomal recessive form of brittle bone disease. Bone. 31:12–18.CrossRefGoogle Scholar
  163. Warman ML, Abbott M, Apte SS, Hefferon T, McIntosh I, Cohn DH, Hecht JT, Olsen BR, Francomano CA (1993) A type X collagen mutation causes Schmid metaphyseal chondrodysplasia. Nat Genet. 5:79–82.CrossRefGoogle Scholar
  164. Watson RB, Wallis GA, Holmes DF, Viljoen D, Byers PH, Kadler KE (1992) Ehlers Danlos syndrome type VIIB. Incomplete cleavage of abnormal type I procollagen by N-proteinase in vitro results in the formation of copolymers of collagen and partially cleaved pNcollagen that are near circular in cross-section. J Biol Chem. 267:9093–9100.Google Scholar
  165. Weil D, Bernard M, Combates N, Wirtz MK, Hollister DW, Steinmann B, Ramirez F (1988) Identification of a mutation that causes exon skipping during collagen pre-mRNA splicing in an Ehlers-Danlos syndrome variant. J Biol Chem. 263:8561–8564.Google Scholar
  166. Weil D, D’Alessio M, Ramirez F, de Wet W, Cole WG, Chan D, Bateman JF (1989a) A base substitution in the exon of a collagen gene causes alternative splicing and generates a structurally abnormal polypeptide in a patient with Ehlers-Danlos syndrome type VII. Embo J. 8: 1705–1710.Google Scholar
  167. Weil D, D’Alessio M, Ramirez F, Steinmann B, Wirtz MK, Glanville RW, Hollister DW (1989b) Temperature-dependent expression of a collagen splicing defect in the fibroblasts of a patient with Ehlers-Danlos syndrome type VII. J Biol Chem. 264:16804–16809.Google Scholar
  168. Weil D, D’Alessio M, Ramirez F, Eyre DR (1990) Structural and functional characterization of a splicing mutation in the pro-alpha 2(I) collagen gene of an Ehlers-Danlos type VII patient. J Biol Chem. 265:16007–16011.Google Scholar
  169. Wenstrup RJ, Florer JB, Davidson JM, Phillips CL, Pfeiffer BJ, Menezes DW, Chervoneva I, Birk DE (2006) Murine model of the Ehlers-Danlos syndrome. col5a1 haploinsufficiency disrupts collagen fibril assembly at multiple stages. J Biol Chem. 281:12888–12895.CrossRefGoogle Scholar
  170. Willing MC, Deschenes SP, Scott DA, Byers PH, Slayton RL, Pitts SH, Arikat H, Roberts EJ (1994) Osteogenesis imperfecta type I: molecular heterogeneity for COL1A1 null alleles of type I collagen. Am J Hum Genet. 55:638–647.Google Scholar
  171. Willing MC, Pruchno CJ, Atkinson M, Byers PH (1992) Osteogenesis imperfecta type I is commonly due to a COL1A1 null allele of type I collagen. Am J Hum Genet. 51:508–515.Google Scholar
  172. Willing MC, Deschenes SP, Slayton RL, Roberts EJ (1996). Premature chain termination is a unifying mechanism for COL1A1 null alleles in osteogenesis imperfecta type I cell strains. Am J Hum Genet. 59:799–809.Google Scholar
  173. Wirtz MK, Rao VH, Glanville RW, Labhard ME, Pretorius PJ, de Vries WN, de Wet WJ, Hollister DW (1993) A cysteine for glycine substitution at position 175 in an alpha 1 (I) chain of type I collagen produces a clinically heterogeneous form of osteogenesis imperfecta. Connect Tissue Res. 29:1–11.CrossRefGoogle Scholar
  174. Zhang Y, Cui FZ, Wang XM, Feng QL, Zhu XD (2002) Mechanical properties of skeletal bone in gene-mutated stopsel(dtl28d) and wild-type zebrafish (Danio rerio) measured by atomic force microscopy-based nanoindentation. Bone. 30:541–546.CrossRefGoogle Scholar
  175. Zhuang J, Tromp G, Kuivaniemi H, Castells S, Prockop DJ (1996) Substitution of arginine for glycine at position 154 of the alpha 1 chain of type I collagen in a variant of osteogenesis imperfecta: comparison to previous cases with the same mutation. Am J Med Genet. 61: 111–116.CrossRefGoogle Scholar
  176. Zolezzi F, Valli M, Clementi M, Mammi I, Cetta G, Pignatti PF, Mottes M (1997) Mutation producing alternative splicing of exon 26 in the COL1A2 gene causes type IV osteogenesis imperfecta with intrafamilial clinical variability. Am J Med Genet. 71:366–370.CrossRefGoogle Scholar
  177. Zumbansen M, Stoffel W (2002) Neutral sphingomyelinase 1 deficiency in the mouse causes no lipid storage disease. Mol Cell Biol. 22:3633–3638.CrossRefGoogle Scholar

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  • R.D. Blank
  • A.L. Boskey

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