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Colony Management

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Advanced Protocols for Animal Transgenesis

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Abstract

Technical advances in the generation of genetically modified (GM) mice and the efforts of large-scale consortia have provided a wealth of resources to the biomedical research community. It has never been easier to obtain a specifically modified allele. However, the establishment and production of GM mouse models using basic breeding methods can still present a unique set of challenges. This chapter aims to equip those new to mouse colony management with some valuable tools. Topics covered include basic reproduction and inheritance, welfare assessment, nomenclature, breeding schemes, and calculators for the production of desired genotypes. Breeding of transgenic founders or chimeras through the first generations is discussed as well as the influence of strain background on this process. Animal records management systems also play an important role in effective colony management.

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Abbreviations

BLASTN:

Basic local alignment search tool for nucleotide sequence comparison

cM:

Centimorgans

CRL:

Charles River Laboratory

ES cell:

Embryonic stem cell

FISH:

Fluorescent in situ hybridization

GM:

Genetically modified

GPL:

General public license

het:

Heterozygous

hom:

Homozyogous

ILAR:

Institute for Laboratory Animal Research

JCMS:

The Jackson Laboratory’s Colony Management System

MACS:

Marker assisted congenic screening

MEF:

Mouse embryonic fibroblast

MGD:

Mouse Genome Database

MGI:

Mouse Genome Informatics

PCR:

Polymerase chain reaction

RFID:

Radio frequency identification

TJL:

The Jackson Laboratory

wt:

Wild type

References

  1. Wells DJ, Playle LC, Enser WEJ, Flecknell PA, Gardiner MA, Holland J, Howard BR, Hubrecht R, Humphreys KR, Jackson IJ, Lane N, Maconochie M, Mason G, Morton DB, Raymond R, Robinson SJA, Watt N (2006) Assessing the welfare of genetically altered mice: working group report. Lab Anim 40:111–114

    Article  PubMed  CAS  Google Scholar 

  2. Thon R, Lassen J, Hansen AK, Jegstrup IM, Ritskes-Hoitinga M (2002) Welfare evaluation of genetically modified mice – an inventory of reports to the Danish Animal Experiments Inspectorate. Scand J Lab Anim Sci 29:45–53

    CAS  Google Scholar 

  3. Buehr M, Hjorth JP, Hansen AK, Sandøe P (2003) Genetically modified laboratory animals – what welfare problems do they face? J Appl Anim Welf Sci 6:319–338

    Article  PubMed  CAS  Google Scholar 

  4. Meisler MH (1992) Insertional mutation of “classical” and novel genes in transgenic mice. Trends Genet 8:341–344

    PubMed  CAS  Google Scholar 

  5. Hughes ED, Qu YY, Genik SJ, Lyons RH, Pacheco CD, Lieberman AP, Samuelson LC, Nasonkin IO, Camper SA, Van Keuren ML, Saunders TL (2007) Genetic variation in C57BL/6 ES cell lines and genetic instability in the Bruce4 C57BL/6 ES cell line. Mamm Genome 18:549–558

    Article  PubMed  CAS  Google Scholar 

  6. Liu X, Wu H, Loring J, Hormuzdi S, Disteche CM, Bornstein P, Jaenisch R (1997) Trisomy eight in ES cells is a common potential problem in gene targeting and interferes with germ line transmission. Dev Dyn 209:85–91

    Article  PubMed  CAS  Google Scholar 

  7. Sugawara A, Goto K, Sotomaru Y, Sofuni T, Ito T (2006) Current status of chromosomal abnormalities in mouse embryonic stem cell lines used in Japan. Comp Med 56:31–34

    PubMed  CAS  Google Scholar 

  8. Kumar RA, Chan KL, Wong AH, Little KQ, Rajcan-Separovic E, Abrahams BS, Simpson EM (2007) Unexpected embryonic stem (ES) cell mutations represent a concern in gene targeting: lessons from "fierce" mice. Genesis 38:51–57

    Article  Google Scholar 

  9. Papaioannau VE, Behringer RR (2005) Mouse phenotypes: a handbook of mutational analysis. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY

    Google Scholar 

  10. Migeon BR (1994) X-chromosome inactivation: molecular mechanisms and genetic consequences. Trends Genet 10:230–235

    Article  PubMed  CAS  Google Scholar 

  11. Schwenk F, Baron U, Rajewsky K (1995) A Cre-transgenic mouse strain for the ubiquitous deletion of loxP-flanked gene segments including deletion in germ cells. Nucleic Acids Res 23:5080–5081

    Article  PubMed  CAS  Google Scholar 

  12. Silver L (1995) Mouse genetics: concepts and applications. Oxford University Press, Oxford

    Google Scholar 

  13. Butler A, Gordon RE, Gatt S, Schuchman EH (2007) Sperm abnormalities in heterozygous acid sphingomyelinase knockout mice reveal a novel approach for the prevention of genetic diseases. Am J Pathol 170:2077–2088

    Article  PubMed  CAS  Google Scholar 

  14. Yan W (2009) Male infertility caused by spermiogenic defects: lessons from gene knockouts. Mol Cell Endocrinol 10:24–32

    Article  Google Scholar 

  15. Hardy P (2004) Gnotobiology and breeding techniques. In: Hedrich H (ed) The laboratory mouse. Elsevier Academic Press, London, UK

    Google Scholar 

  16. Festing M (1999) Introduction to laboratory animal genetics. In: Poole T (ed) The UFAW handbook on the care and management of laboratory animals, 7th edn. Blackwell Science, Oxford, UK, pp 61–93

    Google Scholar 

  17. Nagy A, Gertsenstein M, Vintersten K, Behringer R (2003) Manipulating the mouse embryo: a laboratory manual, 3rd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY

    Google Scholar 

  18. Palmiter RD, Brinster RL (1985) Transgenic mice. Cell 41:343–345

    Article  PubMed  CAS  Google Scholar 

  19. Lois C, Hong EJ, Pease S, Brown EJ, Baltimore D (2002) Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors. Science 295:868–872

    Article  PubMed  CAS  Google Scholar 

  20. Lois C (2006) Generation of transgenic animals using lentiviral vectors. In: Pease S, Lois C (eds) Mammalian and avian transgenesis-new approaches. Springer, Heidelberg, pp 1–22

    Chapter  Google Scholar 

  21. Clark AJ, Bissinger P, Bullock DW, Damak S, Wallace R, Whitelaw CB, Yull F (1994) Chromosomal position effects and the modulation of transgene expression. Reprod Fertil Dev 6:589–598

    Article  PubMed  CAS  Google Scholar 

  22. Liang Z, Breman AM, Grimes BR, Rosen ED (2008) Identifying and genotyping transgene integration loci. Transgenic Res 17:979–983

    Article  PubMed  CAS  Google Scholar 

  23. Matsui S, Sait S, Jones CA, Nowak N, Gross KW (2002) Rapid localization of transgenes in mouse chromosomes with a combined Spectral Karyotyping/FISH technique. Mamm Genome 13:680–685

    Article  PubMed  CAS  Google Scholar 

  24. Wilkie TM, Brinster RL, Palmiter RD (1986) Germline and somatic mosaicism in transgenic mice. Dev Biol 118:9–18

    Article  PubMed  CAS  Google Scholar 

  25. Whitelaw CB, Springbett AJ, Webster J, Clark J (1993) The majority of G0 transgenic mice are derived from mosaic embryos. Transgenic Res 2:29–32

    Article  PubMed  CAS  Google Scholar 

  26. Schwartzberg PL, Goff SP, Robertson EJ (1989) Germ-line transmission of a c-abl mutation produced by targeted gene disruption in ES cells. Science 246:799–803

    Article  PubMed  CAS  Google Scholar 

  27. Nagy A, Rossant J, Nagy R, Abramow-Newerly W, Roder JC (1993) Derivation of completely cell culture-derived mice from early-passage embryonic stem cells. Proc Natl Acad Sci USA 90:8424–8428

    Article  PubMed  CAS  Google Scholar 

  28. Poueymirou WT, Auerbach W, Frendewey D, Hickey JF, Escaravage JM, Esau L, Doré AT, Stevens S, Adams NC, Dominguez MG, Gale NW, Yancopoulos GD, DeChiara TM, Valenzuela DM (2007) F0 generation mice fully derived from gene-targeted embryonic stem cells allowing immediate phenotypic analyses. Nat Biotechnol 25:91–99

    Article  PubMed  CAS  Google Scholar 

  29. Silvers WK (1979) The coat colors of mice: a model for mammalian gene action and interaction. Springer, Heidelberg

    Book  Google Scholar 

  30. Pease S (2006) Ancillary techniques. In: Pease S, Lois C (eds) Mammalian and avian transgenesis-new approaches. Springer, Heidelberg

    Chapter  Google Scholar 

  31. Pettitt SJ, Liang Q, Rairdan XY, Moran JL, Prosser HM, Beier DR, Lloyd KC, Bradley A, Skarnes WC (2009) Agouti C57BL/6N embryonic stem cells for mouse genetic resources. Nat Meth 6:493–495

    Article  CAS  Google Scholar 

  32. Auerbach AB, Norinsky R, Ho W, Losos K, Guo Q, Chatterjee S, Joyner AL (2003) Strain-dependent differences in the efficiency of transgenic mouse production. Transgenic Res 12:59–69

    Article  PubMed  CAS  Google Scholar 

  33. Simpson EM, Linder CC, Sargent EE, Davisson MT, Mobraaten LE, Sharp JJ (1997) Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice. Nat Genet 16:19–27

    Article  PubMed  CAS  Google Scholar 

  34. Seong ES, Saunders TL, Stewart CL, Burmeister M (2004) To knockout in 129 or in C57BL/6: that is the question. Trends Genet 20:59–62

    Article  PubMed  CAS  Google Scholar 

  35. Noben-Trauth N, Köhler G, Bürki K, Ledermann B (1996) Efficient targeting of the IL-4 gene in a BALB/c embryonic stem cell line. Transgenic Res 5:487–491

    Article  PubMed  CAS  Google Scholar 

  36. Silva AJ, Simpson EM, Takahashi JS, Lipp H-P, Nakanishi S, Wehner JM, Giese KP, Tully T, Abel T, Chapman PF, Fox K, Grant S, Itohara S, Lathe R, Mayford M, McNamara JO, Morris RJ, Picciotto M, Roder J, Shin H-S, Slesinger PA, Storm DR, Stryker MP, Tonegawa S, Wang Y, Wolfer DP (1997) Mutant mice and neuroscience: recommendations concerning genetic background. Banbury Conference on genetic background in mice. Neuron 19:755–759

    Article  Google Scholar 

  37. Lander ES, Schork NJ (1994) Genetic dissection of complex traits. Science 265:2037–2048

    Article  PubMed  CAS  Google Scholar 

  38. Wakeland E, Morel L, Achey K, Yui M, Longmate J (1997) Speed congenics: a classic technique in the fast lane (relatively speaking). Immunol Today 18:472–477

    Article  PubMed  CAS  Google Scholar 

  39. Petkov PM, Cassell MA, Sargent EE, Donnelly CJ, Robinson P, Crew V, Asquith S, Haar RV, Wiles MV (2004) Development of a SNP genotyping panel for genetic monitoring of the laboratory mouse. Genomics 83:902–911

    Article  PubMed  CAS  Google Scholar 

  40. Weil MM, Brown BW, Serachitopol DM (1997) Genotype selection to rapidly breed congenic strains. Genetics 146:1061–1069

    PubMed  CAS  Google Scholar 

  41. Armstrong NJ, Brodniki TC, Speed TP (2006) Mind the gap: analysis of marker-assisted breeding strategies for inbred mouse strains. Mamm Genome 17:273–287

    Article  PubMed  Google Scholar 

  42. Markel P, Shu P, Ebeling C, Carlson GA, Nagle DL, Smutko JS, Moore KJ (1997) Theoretical and empirical issues for marker-assisted breeding of congenic mouse strains. Nat Genet 178:280–284

    Article  Google Scholar 

  43. Ogonuki N, Inoue K, Hirose M, Miura I, Mochida K, Sato T, Mise N, Mekada K, Yoshiki A, Abe K, Kurihara H, Wakana S, Ogura A (2009) A high-speed congenic strategy using first-wave male germ cells. PLoS ONE 4(3):e4943

    Article  PubMed  Google Scholar 

  44. Schmitt AO, Bortfeldt R, Neuschl C, Brockmann GA (2009) RandoMate: a program for the generation of random mating schemes for small laboratory animals. Mamm Genome 20:321–325

    Article  PubMed  Google Scholar 

  45. Mäkinen V-P, Parkkonen M, Wessman M, Groop P-H, Kanninen T, Kaski K (2005) High-throughput pedigree drawing. Eur J Hum Genet 13:987–989

    Article  PubMed  Google Scholar 

  46. Giraldo P, Montoliu L (2001) Size matters: use of YACs, BACs and PACs in transgenic animals. Transgenic Res 2:83–103

    Google Scholar 

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Acknowledgements

The author would like to thank the following people for their generous assistance in preparing this chapter: Ruth Arkell, Michael Dobbie, Holger Maier, Kristina Nagy, Thomas Preiss, and Duncan Sparrow.

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Correspondence to Karen Brennan .

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Brennan, K. (2011). Colony Management. In: Pease, S., Saunders, T. (eds) Advanced Protocols for Animal Transgenesis. Springer Protocols Handbooks. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-20792-1_22

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  • DOI: https://doi.org/10.1007/978-3-642-20792-1_22

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  • Print ISBN: 978-3-642-20791-4

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