A Nonsynonymous Substitution of Leads to Changes in Body Size in Dogs and Mice.

is a LIM-homeodomain transcription factor that affects body size in mammals by regulating the secretion of pituitary hormones. Akita, Shiba Inu, and Mame Shiba Inu dogs are Japanese native dog breeds that have different body sizes. To determine whether plays a role in the differing body sizes of these three dog breeds, we sequenced the gene in the three breeds, which led to the identification of an SNP in codon 280 (S280N) associated with body size. The allele frequency at this SNP differed significantly between the large Akita and the two kinds of smaller Shiba dogs. To validate the function of this SNP on body size, we introduced this change into the gene of mice. Homozygous mutant mice (S279N) were found to have significantly increased body lengths and weights compared to heterozygous mutant (S279N) and wild-type (S279N) mice several weeks after weaning. These results demonstrate that a nonsynonymous substitution in plays an important role in regulating body size in mammals.