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Rat Genomics pp 243-266 | Cite as

Generation of Congenic and Consomic Rat Strains

  • Dominique Lagrange
  • Gilbert J Fournié
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 597)

Abstract

Congenic and consomic rat strains are inbred strains containing in their genome a given genomic region (congenic) or a whole chromosome (consomic) from another strain. They are nowadays invaluable tools for the identification of genes and mechanisms of multifactorial diseases, one of the main goals in biomedicine. They are produced by repeated backcrosses from a donor inbred strain to a recipient inbred strain, and thereafter maintained by conventional brother-x-sister mating. Although their production is lengthy and costly, it only requires a zootechny unit for breeding and tools for genotyping.

Key words

Congenic rat Consomic rat Genetic dissection Complex traits Quantitative trait locus Positional cloning Polygenic disease 

Notes

Acknowledgements

The authors want to thanks the following participants in the works done on rat congenics in our laboratory: Pr Philippe Druet, who has initiated the work on rat genomics; Dr Abdelhadi Saoudi, who has collaborated in most of the studies; Dr Dominique Gauguier, who has helped us to create the first congenic strains; all the students who have participated in the construction of congenic strains and sub-strains, particularly Drs Magali Mas, Jean-François Subra, Pierre Cavaillès, Céline Colacios and Olivier Papapietro and all the persons who are or have been in care of the rats in our Zootechnic unit, particularly Mrs Maryline Calise, Sylvie Appolinaire, Audrey Boyer, Marie-Andrée Daussion, Corinne Senty, Carine Segui, Magali Toulouse, Aline Tridon, Mr. Patrick Aregui, Thierry Ruiz.

The development of the congenic strains in our laboratory has been supported by grants from Institut National de la Santé et de la Recherche Médicale (INSERM), Genopole® Toulouse Midi-Pyrénées (GenoToul), Agence Nationale de Recherche (ANR), Fondation pour la Recherche Médicale (FRM), Association de Recherche sur la Polyarthrite Rhumatoïde (ARP) and Fondation Arthritis Courtin, Association de Recherche sur la Sclérose en Plaques (ARSEP), Association Française contre les Myopathies (AFM), Etablissement Français des Greffes (EFG), Ligue Contre le Cancer (LCC), Université Paul Sabatier (UPS), Région Midi-Pyrénées, Ministère de l’Aménagement du Territoire et de l’Environnement and Ministère Délégué à la Recherche et aux Nouvelles Technologies.

References

  1. 1.
    Snell GD (1964) Methods for study of histocompatibility genes and isoantigens. Methods Med Res 10:1–7PubMedGoogle Scholar
  2. 2.
    Cowley AW Jr, Liang M, Roman RJ, Greene AS, Jacob HJ (2004) Consomic rat model systems for physiological genomics. Acta Physiol Scand 181:585–592CrossRefPubMedGoogle Scholar
  3. 3.
    Lander ES, Schork NJ (1994) Genetic dissection of complex traits. Science 265:2037–2048CrossRefPubMedGoogle Scholar
  4. 4.
    Darvasi A (1998) Experimental strategies for the genetic dissection of complex traits in animal models. Nat Genet 18:19–24CrossRefPubMedGoogle Scholar
  5. 5.
    Wakeland E, Morel L, Achey K, Yui M, Longmate J (1997) Speed congenics: a classic technique in the fast lane (relatively speaking). Immunol Today 18:472–477CrossRefPubMedGoogle Scholar
  6. 6.
    Gregorova S, Divina P, Storchova R, Trachtulec Z, Fotopulosova V, Svenson KL, Donahue LR, Paigen B, Forejt J (2008) Mouse consomic strains: exploiting genetic divergence between Mus m. musculus and Mus m. domesticus subspecies. Genome Res 18:509–515CrossRefPubMedGoogle Scholar
  7. 7.
    Singer JB, Hill AE, Burrage LC, Olszens KR, Song J, Justice M, O’Brien WE, Conti DV, Witte JS, Lander ES, Nadeau JH (2004) Genetic dissection of complex traits with chromosome substitution strains of mice. Science 304:445–448CrossRefPubMedGoogle Scholar
  8. 8.
    Takada T, Mita A, Maeno A, Sakai T, Shitara H, Kikkawa Y, Moriwaki K, Yonekawa H, Shiroishi T (2008) Mouse inter-subspecific consomic strains for genetic dissection of quantitative complex traits. Genome Res 18:500–508CrossRefPubMedGoogle Scholar
  9. 9.
    Dwinell MR, Forster HV, Petersen J, Rider A, Kunert MP, Cowley AW Jr, Jacob HJ (2005) Genetic determinants on rat chromosome 6 modulate variation in the hypercapnic ventilatory response using consomic strains. J Appl Physiol 98:1630–1638CrossRefPubMedGoogle Scholar
  10. 10.
    Kunert MP, Drenjancevic-Peric I, Dwinell MR, Lombard JH, Cowley AW Jr, Greene AS, Kwitek AE, Jacob HJ (2006) Consomic strategies to localize genomic regions related to vascular reactivity in the Dahl salt-sensitive rat. Physiol Genomics 26:218–225CrossRefPubMedGoogle Scholar
  11. 11.
    Kunert MP, Dwinell MR, Drenjancevic-Peric I, Lombard JH (2008) Sex-specific differences in chromosome-dependent regulation of vascular reactivity in female consomic rat strains from a SS × BN cross. Am J Physiol Regul Integr Comp Physiol 295(2):R516–R527PubMedGoogle Scholar
  12. 12.
    Schulz A, Weiss J, Schlesener M, Hansch J, Wehland M, Wendt N, Kossmehl P, Sietmann A, Grimm D, Stoll M, Nyengaard JR, Kreutz R (2007) Development of overt proteinuria in the Munich Wistar Fromter rat is suppressed by replacement of chromosome 6 in a consomic rat strain. J Am Soc Nephrol 18:113–121CrossRefPubMedGoogle Scholar
  13. 13.
    Nicklas W, Baneux P, Boot R, Decelle T, Deeny AA, Fumanelli M, Illgen-Wilcke B (2002) Recommendations for the health monitoring of rodent and rabbit colonies in breeding and experimental units. Lab Anim 36:20–42CrossRefPubMedGoogle Scholar
  14. 14.
    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 17:280–284CrossRefPubMedGoogle Scholar
  15. 15.
    Weil MM, Brown BW, Serachitopol DM (1997) Genotype selection to rapidly breed congenic strains. Genetics 146:1061–1069PubMedGoogle Scholar
  16. 16.
    Saar K, Beck A, Bihoreau MT, Birney E, Brocklebank D, Chen Y, Cuppen E, Demonchy S, Dopazo J, Flicek P, Foglio M, Fujiyama A, Gut IG, Gauguier D, Guigo R, Guryev V, Heinig M, Hummel O, Jahn N, Klages S, Kren V, Kube M, Kuhl H, Kuramoto T, Kuroki Y, Lechner D, Lee YA, Lopez-Bigas N, Lathrop GM, Mashimo T, Medina I, Mott R, Patone G, Perrier-Cornet JA, Platzer M, Pravenec M, Reinhardt R, Sakaki Y, Schilhabel M, Schulz H, Serikawa T, Shikhagaie M, Tatsumoto S, Taudien S, Toyoda A, Voigt B, Zelenika D, Zimdahl H, Hubner N (2008) SNP and haplotype mapping for genetic analysis in the rat. Nat Genet 40:560–566CrossRefPubMedGoogle Scholar
  17. 17.
    Lohmiller J, Swing S (2006) Reproduction and breeding. In: Mark AS, Steven HW, Craig LF (eds) The laboratory rat, Elsevier, Amsterdam, pp. 154–156Google Scholar
  18. 18.
    Christian JJ, Lemunyan CD (1958) Adverse effects of crowding on lactation and reproduction of mice and two generations of their progeny. Endocrinology 63:517–529CrossRefPubMedGoogle Scholar
  19. 19.
    Olofsson P, Johansson A, Wedekind D, Kloting I, Klinga-Levan K, Lu S, Holmdahl R (2004) Inconsistent susceptibility to autoimmunity in inbred LEW rats is due to genetic crossbreeding involving segregation of the arthritis-regulating gene Ncf1. Genomics 83:765–771CrossRefPubMedGoogle Scholar
  20. 20.
    Hall J, Nanthakumar E (2001) Automated fluorescent genotyping. Curr Protoc Hum Genet Chapter 2: Unit 2.8Google Scholar
  21. 21.
    Behringer R (1998) Supersonic congenics? Nat Genet 18:108CrossRefPubMedGoogle Scholar
  22. 22.
    Nadeau JH, Singer JB, Matin A, Lander ES (2000) Analysing complex genetic traits with chromosome substitution strains. Nat Genet 24:221–225CrossRefPubMedGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.INSERM, U563ToulouseFrance
  2. 2.Université Toulouse III Paul Sabatier, Institut Claude de Préval (IFR30)ToulouseFrance

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