Advertisement

Structural Integration of Cerebellar Grafts in Ataxic Mouse Mutants

  • Lazaros C. Triarhou
Part of the Neuroscience Intelligence Unit book series (NIU.LANDES)

Abstract

There are many mutations in the laboratory mouse that interfere with the formation and maintenance of the cerebellar circuitry (refs. 1, 2 and chapter 4 in this book). The cerebellar lesion may consist in either defective positioning of specific neuronal populations or selective loss. Such mutations provide unique material for investigating developmental and degenerative events because: (i) the background on the cellular architecture and synaptic connections of the cerebellum is strong; (ii) the cerebellum is a relatively simple neuronal circuit for studying phenomena with general implications for the CNS and (iii) the molecular genetics and chromosomal structure have been characterized in the laboratory mouse better than in any other mammal. In addition to insight into cerebellar ontogeny, neurological mutants offer invaluable experimental models pertinent to the neuropathological lesions of the human cerebellar ataxias. A description of cerebellar transplantation studies in cerebellar mutants (Table 7.1) addressing various issues follows.

Keywords

Purkinje Cell Cerebellar Ataxia Deep Cerebellar Nucleus Dorsal Cochlear Nucleus Anat Embryol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Sidman RL. Mutations affecting the central nervous system in the mouse. In: Schmitt FO, Bird SJ, Bloom FE. Molecular Genetic Neuroscience. New York: Raven Press, 1982: 389–400.Google Scholar
  2. 2.
    Sidman RL, Green MC, Appel SH. Catalog of the Neurological Mutants of the Mouse. Cambridge, MA: Harvard University Press, 1965.Google Scholar
  3. 3.
    Sidman RL, Lane PW, Dickie MM. Staggerer, a new mutation in the mouse affecting the cerebellum. Science 1962; 137: 610–612.PubMedCrossRefGoogle Scholar
  4. 4.
    Sotelo C, Changeux J-P. Transsynaptic degeneration `en cascade’ in the cerebellar cortex of staggerer mutant mice. Brain Res 1974; 67: 519–526.PubMedCrossRefGoogle Scholar
  5. 5.
    Hatten ME, Messer A. Postnatal cerebellar cells from staggerer mutant mice express embryonic cell surface characteristics. Nature (Lond) 1978; 276: 504–506.CrossRefGoogle Scholar
  6. 6.
    Trenkner E. Postnatal cerebellar cells of staggerer mutant mice express immature components on their surface. Nature (Lond) 1979; 277: 566–567.CrossRefGoogle Scholar
  7. 7.
    Wille W, Heinlein UAO, Spier-Michl I et al. Development-dependent regulation of N-acetyl-ß-D-hexosaminidase of cerebellum and cerebrum of normal and staggerer mutant mice. J Neurochem 1983; 40: 235–239.PubMedCrossRefGoogle Scholar
  8. 8.
    Wille W, Trenkner E. Changes in particulate neuraminidase activity during normal and staggerer mutant mouse development. J Neurochem 1981; 37: 443–446.PubMedCrossRefGoogle Scholar
  9. 9.
    Edelman GM, Chuong C-M. Embryonic to adult conversion of neural cell adhesion molecules in normal and staggerer mice. Proc Natl Acad Sci USA 1982; 79: 7036–7040.PubMedCrossRefGoogle Scholar
  10. 10.
    Wille W, Goldowitz D, Seiger A et al. The neurological mutation staggerer is expressed in embryonic cerebellar transplants matured in the anterior eye chamber of normal mice. Neurosci Lett 1983; 42: 1–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Davisson MT, Roderick TH. Linkage map. In: Lyon MF, Searle AG, eds. Genetic Variants and Strains of the Laboratory Mouse. 2nd ed. Oxford, Stuttgart: Oxford University Press, Gustav Fischer Verlag, 1989: 416–427.Google Scholar
  12. 12.
    Rakic P, Sidman RL. Sequence of developmental abnormalities leading to granule cell deficit in cerebellar cortex of weaver mutant mice. J Comp Neurol 1973; 152: 103–132.PubMedCrossRefGoogle Scholar
  13. 13.
    Sotelo C. Mutant mice and the formation of cerebellar circuitry. Trends Neurosci 1980; 3: 33–36.CrossRefGoogle Scholar
  14. 14.
    Triarhou LC. Weaver gene expression in central nervous system. In: Conn PM, ed. Gene Expression in Neural Tissues. San Diego: Academic Press, 1992: 209–227.Google Scholar
  15. 15.
    Triarhou LC, Ghetti B, Low WC. Purkinje and granule cells survive in cerebellar grafts implanted into hosts with genetically-determined Purkinje or granule cell degeneration. Ann Neurol 1986; 20: 138.Google Scholar
  16. 16.
    Low WC, Triarhou LC, Ghetti B. Cerebellar transplants into mutant mice with Purkinje and granule cell degeneration. Ann NY Acad Sci 1987; 495: 740–744.CrossRefGoogle Scholar
  17. 17.
    Triarhou LC, Low WC, Ghetti B. Transplantation of cerebellar anlagen to hosts with genetic cerebellocortical atrophy. Anat Embryol (Berl) 1987; 176: 145–154.CrossRefGoogle Scholar
  18. 18.
    Takayama H, Kohsaka S, Shinozaki T et al. Immunohistochemical studies on synapse formation by embryonic cerebellar tissue transplanted into the cerebellum of the weaver mutant mouse. Neurosci Lett 1987; 79: 246–250.PubMedCrossRefGoogle Scholar
  19. 19.
    Takayama H, Toya S, Shinozaki T et al. Possible synapse formation by embryonic cerebellar tissue grafted into the cerebellum of the weaver mutant mouse. Acta Neurochir [Suppl] 1988; 43: 154–158.Google Scholar
  20. 20.
    Gao W-Q, Hatten ME. Neuronal differentiation rescued by implantation of weaver granule cell precursors into wild-type cerebellar cortex. Science 1993; 260: 367–370.PubMedCrossRefGoogle Scholar
  21. 21.
    Goldowitz D. The weaver granuloprival phenotype is due to intrinsic action of the mutant locus in granule cells: Evidence from homozygous weaver chimeras. Neuron 1989; 2: 1565–1575.PubMedCrossRefGoogle Scholar
  22. 22.
    Mullen RJ, Eicher EM, Sidman RL. Purkinje cell degeneration, a new neurological mutation in the mouse. Proc Natl Acad Sci USA 1976; 73: 208–212.PubMedCrossRefGoogle Scholar
  23. 23.
    Mullen RJ. Site of pcd gene action and Purkinje cell mosaicism in the cerebella of chimeric mice. Nature (Lond) 1977; 270: 245–247.CrossRefGoogle Scholar
  24. 24.
    Landis SC, Mullen RJ. The development and degeneration of Purkinje cells in pcd mutant mice. J Comp Neurol 1978; 177: 125–144.PubMedCrossRefGoogle Scholar
  25. 25.
    Ghetti B, Triarhou LC. The Purkinje cell degeneration mutant: A model to study the consequences of neuronal degeneration. In: Plaitakis A, ed. Cerebellar Degenerations: Clinical Neurobiology. Boston: Kluwer Academic, 1992: 159–181.CrossRefGoogle Scholar
  26. 26.
    Triarhou LC, Norton J, Ghetti B. Anterograde transsynaptic degeneration in the deep cerebellar nuclei of Purkinje cell degeneration (pcd) mutant mice. Exp Brain Res 1987; 66: 577–588.PubMedCrossRefGoogle Scholar
  27. 27.
    Triarhou LC, Ghetti B. Stabilisation of neurone number in the inferior olivary complex of aged `Purkinje cell degeneration’ mutant mice. Acta Neuropathol (Berl) 1991; 81: 597–602.CrossRefGoogle Scholar
  28. 28.
    Triarhou LC, Norton J, Alyea C et al. A quantitative study of the granule cells in the Purkinje cell degeneration (pcd) mutant. Ann Neurol 1985; 18: 146.Google Scholar
  29. 29.
    Triarhou LC, Ghetti B. Monoaminergic nerve terminals in the cerebellar cortex of Purkinje cell degeneration mutant mice: Fine structural integrity and modification of cellular environs following loss of Purkinje and granule cells. Neuroscience 1986; 18: 795–807.PubMedCrossRefGoogle Scholar
  30. 30.
    Triarhou LC, Ghetti B. Serotonin immunoreactivity in the cerebellum of two neurological mutant mice and the corresponding wild-type genetic stocks. J Chem Neuroanat 1991; 4: 421–428.PubMedCrossRefGoogle Scholar
  31. 31.
    Alvarado-Mallart RM, Sotelo C. Cerebellar grafting in murine heredodegenerative ataxia. Current limitations for a therapeutic approach. Adv Neurol 1993; 61: 181–192.PubMedGoogle Scholar
  32. 32.
    Gardette R, Alvarado-Mallart RM, Crepel F, Sotelo C. Electrophysiological demonstration of a synaptic integration of transplanted Purkinje cells into the cerebellum of the adult Purkinje cell degeneration mutant mouse. Neuroscience 1988; 24: 777–789.PubMedCrossRefGoogle Scholar
  33. 33.
    Gardette R, Crepel F, Alvarado-Mallart RM et al. Fate of grafted embryonic Purkinje cells in the cerebellum of the adult “Purkinje cell degeneration” mutant mouse. II. Development of synaptic responses: An in vitro study. J Comp Neurol 1990; 295: 188–196.PubMedCrossRefGoogle Scholar
  34. 34.
    Keep M, Alvarado-Mallart RM, Sotelo C. New insights on the factors orienting the axonal outgrowth of grafted Purkinje cells in the pcd cerebellum. Dev Neurosci 1992; 14: 153–165.PubMedCrossRefGoogle Scholar
  35. 35.
    Sotelo C. Transplantation de neurones embryonnaires dans le cervelet de souris: Restauration de l’ intégrité cérébelleuse chez des souris avec ataxie hérédo-dégénérative. Méd Sci 1988; 8: 507–514.Google Scholar
  36. 36.
    Sotelo C. Cerebellar synaptogenesis: Mutant mice—neuronal grafting. J Physiol (Paris) 1991; 85: 134–144.Google Scholar
  37. 37.
    Sotelo C. Cell interactions underlying Purkinje cell replacement by neural grafting in the pcd mutant cerebellum. Can J Neurol Sci 1993; 20 [Suppl 3]: S43 - S52.PubMedGoogle Scholar
  38. 38.
    Sotelo C, Alvarado-Mallart RM. Growth and differentiation of cerebellar suspensions transplanted into the adult cerebellum of mice with heredodegenerative ataxia. Proc Natl Acad Sci USA 1986; 83: 1135–1139.PubMedCrossRefGoogle Scholar
  39. 39.
    Sotelo C, Alvarado-Mallart RM. Cerebellar transplantations in adult mice with heredo-degenerative ataxia. Ann NY Acad Sci 1987; 495: 242–266.PubMedCrossRefGoogle Scholar
  40. 40.
    Sotelo C, Alvarado-Mallart RM. Embryonic and adult neurons interact to allow Purkinje cell replacement in mutant cerebellum. Nature (Lond) 1987; 327: 421–423.CrossRefGoogle Scholar
  41. 41.
    Sotelo C, Alvarado-Mallart RM. Reconstruction of the defective cerebellar circuitry in adult Purkinje cell degeneration mutant mice by Purkinje cell replacement through transplantation of solid embryonic implants. Neuroscience 1987; 20: 1–22.PubMedCrossRefGoogle Scholar
  42. 42.
    Sotelo C, Alvarado-Mallart RM. Integration of grafted Purkinje cells into the host cerebellar ciruitry in Purkinje cell degeneration mutant mouse. Prog Brain Res 1988; 78: 141–154.PubMedCrossRefGoogle Scholar
  43. 43.
    Sotelo C, Alvarado-Mallart RM. The reconstruction of cerebellar circuits. Trends Neurosci 1991; 14: 350–355.PubMedCrossRefGoogle Scholar
  44. 44.
    Sotelo C, Alvarado-Mallart RM. Cerebellar grafting as a tool to analyze new aspects of cerebellar development and plasticity. In: Hinds R, Sotelo C, eds. The Cerebellum Revisited. New York-Berlin-Heidelberg: Springer-Verlag, 1992: 84–115.CrossRefGoogle Scholar
  45. 45.
    Sotelo C, Alvarado-Mallart RM, Frain M et al. Molecular plasticity of adult Bergmann fibers is associated with radial migration of grafted Purkinje cells. J Neurosci 1994; 14: 124–133.PubMedGoogle Scholar
  46. 46.
    Sotelo C, Alvarado-Mallart RM, Gardette R et al. Fate of grafted embryonic Purkinje cells in the cerebellum of the adult “Purkinje cell degeneration” mutant mouse. I. Development of reciprocal graft-host interactions. J Comp Neurol 1990; 295: 165–187.PubMedCrossRefGoogle Scholar
  47. 47.
    Sotelo C, Alvarado-Mallart RM, Keep M. Fate of axons of embryonic Purkinje cells grafted in the adult cerebellum of the pcd mutant mouse. In: Letourneau PC, Kater SB, Macagno ER, eds. The Nerve Growth Cone. New York: Raven Press, 1992: 505–517.Google Scholar
  48. 48.
    Chang AC, Triarhou LC, Alyea CJ et al. Developmental expression of polypeptide PEP-19 in cerebellar suspensions transplanted into the cerebellum of pcd mutant mice. Exp Brain Res 1989; 76: 639–645.PubMedCrossRefGoogle Scholar
  49. 49.
    Ghetti B, Triarhou LC, Alyea CJ et al. Timing of neuronal replacement in cerebellar degenerative ataxia of Purkinje cell type. Prog Brain Res 1990; 82: 197–202.PubMedCrossRefGoogle Scholar
  50. 50.
    Triarhou LC. Cerebellar transplantation in hereditary ataxia and the recovery of function: Why do the deep cerebellar nuclei represent a better graft site than the cerebellar cortex. Abstr Am Soc Neural Transpl 1995; 2: 21.Google Scholar
  51. 51.
    Triarhou LC, Low WC, Ghetti B. Intraparenchymal grafting of cerebellar cell suspensions to the deep cerebellar nuclei of pcd mutant mice: Rationale and histochemical organization. Soc Neurosci Abstr 1989; 15: 10.Google Scholar
  52. 52.
    Triarhou LC, Low WC, Ghetti B. Intraparenchymal grafting of cerebellar cell suspensions to the deep cerebellar nuclei of pcd mutant mice, with particular emphasis on re-establishment of a Purkinje cell cortico-nuclear projection. Anat Embryol (Berl) 1992; 185: 409–420.CrossRefGoogle Scholar
  53. 53.
    Triarhou LC, Low WC, Ghetti B. Serotonin fiber innervation of cerebellar cell suspensions intraparenchymally grafted to the cerebellum of pcd mutant mice. Neurochem Res 1992; 17: 475–482.PubMedCrossRefGoogle Scholar
  54. 54.
    Triarhou LC, Zhang W, Lee W-H. Graft-induced restoration of function in hereditary cerebellar ataxia. Neuroreport 1995; 6: 1827–1832.PubMedCrossRefGoogle Scholar
  55. 55.
    Triarhou LC, Zhang W, Lee W-H. Amelioration of the behavioral phenotype in genetically ataxic mice through bilateral intracerebellar grafting of fetal Purkinje cells. Cell Transpl 1996; 5: 269–277.CrossRefGoogle Scholar
  56. 56.
    Zhang W, Lee W-H, Triarhou, L.C. Grafted cerebellar cells in a mouse model of hereditary ataxia express IGF-I system genes and partially restore behavioral function. Nature Med 1996; 2: 65–71.PubMedCrossRefGoogle Scholar
  57. 57.
    Sidman RL, Green MC. `Nervous’, a new mutant mouse with cerebellar disease. In: Sabourdy M, ed. Les Mutants Pathologiques chez l’ Animal. Paris: Éditions du Centre National de la Recherche Scientifique, 1970: 69–79.Google Scholar
  58. 58.
    Landis SC. Ultrastructural changes in the mitochondria of cerebellar Purkinje cells of nervous mutant mice. J Cell Biol 1973; 57: 782–797.PubMedCrossRefGoogle Scholar
  59. 59.
    Phillips RJS. “Lurcher”, a new gene in linkage group XI of the house mouse. J Genet 1960; 57:35–42.Google Scholar
  60. 60.
    Caddy KWT, Biscoe TJ. Structural and quantitative studies in the normal C3H and Lurcher mutant mouse. Phil Trans Roy Soc Lond (Biol) 1979; 287: 167–201.CrossRefGoogle Scholar
  61. 61.
    Tomey DA, Heckroth JA. Transplantation of normal embryonic cerebellar cell suspensions into the cerebellum of Lurcher mutant mice. Exp Neurol 1993; 122: 165–170.PubMedCrossRefGoogle Scholar
  62. 62.
    Dumesnil-Bousez N, Sotelo C. Partial reconstruction of the adult Lurcher cerebellar circuitry by neural grafting. Neuroscience 1993; 55: 1–21.PubMedCrossRefGoogle Scholar
  63. 63.
    Altman J. Morphological development of the rat cerebellum and some of its mechanisms. Exp Brain Res [Suppl] 1982; 6: 8–49.CrossRefGoogle Scholar
  64. 64.
    Dumesnil-Bousez N, Sotelo C. The dorsal cochlear nucleus of the adult Lurcher mouse is specifically invaded by embryonic grafted Purkinje cells. Brain Res 1993; 622: 343–347.PubMedCrossRefGoogle Scholar
  65. 65.
    Mugnaini E, Morgan JI. The neuropeptide cerebellin is a marker for two similar neuronal circuits in rat brain. Proc Natl Acad Sci USA 1987; 84: 8692–8696.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • Lazaros C. Triarhou
    • 1
  1. 1.Indiana University School of MedicineIndianapolisUSA

Personalised recommendations