International Mammalian Genome Society

The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

E8 Introgressing Mus spretus Genome into a C57BL/6 Background: Lessons from the Establishment of Interspecific Recombinant Congenic Strains

Xavier Montagutelli, Stéphanie Voegeling, Marek Szatanik, Jean-Louis Guénet. Unité de Génétique des Mammifères, Institut Pasteur, 25 rue du Docteur Roux - 75724 PARIS CEDEX 15

It is well known that the two main subspecies of Mus musculus, i.e. M.m. musculus and M.m. domesticus are found in different geographical areas with a border extending from Denmark to Bulgaria. Along this border, there is continuous production of intersubspecific hybrids within a narrow band known as hybrid zone. Several groups have shown that gene exchange is very limited, with hybrid progeny having reduced fitness. Although natural hybrids between M.m. domesticus and M. spretus have not been observed, these can be produced under laboratory conditions. Such crosses have been very useful in the establishment of high resolution, high density, genetic maps in the mouse. We have developed, over the last ten years, a set of over 50 interspecific recombinant congenic strains with C57BL/6 as the recipient strain, and SEG/Pas as the donor strain, as a tool to analyze the genetics of complex traits. According to the breeding scheme, we expected that the contribution of M. spretus genome be around 9% overall. These strains were genotyped after 8 generations of inbreeding and after 22 generations of inbreeding (mean values), for over 200 loci. The data obtained show that, although no selection was performed during the inbreeding process, the final percentage of spretus genome found in the strains is only 1.6%, over 5 times less than expected. This percentage decreases with the number of inbreeding generations during the first 12 generations, suggesting that spretus alleles were repeatedly selected against in heterozygous mice. This is confirmed by the fact that most strains that were segregating for both alleles at a given locus at F8 were found to have retained the B6 allele at F22. These data show that introgression of M. spretus into M.m. domesticus, although possible, is compatible with fertility only when limited to a small number of genomic regions. We hypothesize that this is mainly due to numerous epistatic interactions.


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