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Intersubspecific subcongenic mouse strain analysis reveals closely linked QTLs with opposite effects on body weight

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Abstract

A previous genome-wide QTL study revealed many QTLs affecting postnatal body weight and growth in an intersubspecific backcross mouse population between the C57BL/6J (B6) strain and wild Mus musculus castaneus mice captured in the Philippines. Subsequently, several closely linked QTLs for body composition traits were revealed in an F2 intercross population between B6 and B6.Cg-Pbwg1, a congenic strain on the B6 genetic background carrying the growth QTL Pbwg1 on proximal chromosome 2. However, no QTL affecting body weight has been duplicated in the F2 population, except for mapping an overdominant QTL that causes heterosis of body weight. In this study, we developed 17 intersubspecific subcongenic strains with overlapping and nonoverlapping castaneus regions from the B6.Cg-Pbwg1 congenic strain in order to search for and genetically dissect QTLs affecting body weight into distinct closely linked loci. Phenotypic comparisons of several developed subcongenic strains with the B6 strain revealed that two closely linked but distinct QTLs that regulate body weight, named Pbwg1.11 and Pbwg1.12, are located on an 8.9-Mb region between D2Mit270 and D2Mit472 and on the next 3.6-Mb region between D2Mit205 and D2Mit182, respectively. Further analyses using F2 segregating populations obtained from intercrosses between B6 and each of the two selected subcongenic strains confirmed the presence of these two body weight QTLs. Pbwg1.11 had an additive effect on body weight at 6, 10, and 13 weeks of age, and its castaneus allele decreased it. In contrast, the castaneus allele at Pbwg1.12 acted in a dominant fashion and surprisingly increased body weight at 6, 10, and 13 weeks of age despite the body weight of wild castaneus mice being 60% of that of B6 mice. These findings illustrate the complex genetic nature of body weight regulation and support the importance of subcongenic mouse analysis to dissect closely linked loci.

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Acknowledgments

M. B. R. Mollah was supported by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) Scholarship of Japanese Government. This work was supported by Grants-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science to A. Ishikawa.

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  1. Laboratory of Animal Genetics, Division of Applied Genetics and Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya, Aichi, 464-8601, Japan

    Md. Bazlur R. Mollah & Akira Ishikawa

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  1. Md. Bazlur R. Mollah
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  2. Akira Ishikawa
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Correspondence to Akira Ishikawa.

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Supplementary material 1 (DOC 79 kb)

335_2011_9323_MOESM2_ESM.pdf

Supplementary Fig. 1. Construction of 17 subcongenic strains for the growth QTL Pbwg1 on mouse Chr 2. The black bar indicates the minimum genomic region derived from the M. m. castaneus mouse, and the gray bar indicates the region from the B6 mouse. The hatched bar indicates a gray zone where recombination occurred. Distal and proximal borders of each subcongenic strain are arbitrarily drawn by vertical lines. Physical map positions (Mb) of microsatellite markers are shown on the horizontal line (Supplementary Table 1). Size (Mb) indicates the minimum length of the castaneus donor region.(PDF 431 kb)

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Mollah, M.B.R., Ishikawa, A. Intersubspecific subcongenic mouse strain analysis reveals closely linked QTLs with opposite effects on body weight. Mamm Genome 22, 282–289 (2011). https://doi.org/10.1007/s00335-011-9323-9

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