PDF(Pubmed)
Abstract：
Lhx3 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 Lhx3 plays a role in the differing body sizes of these three dog breeds, we sequenced the Lhx3 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 Lhx3 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 Lhx3 plays an important role in regulating body size in mammals.
摘要：
Lhx3是LIM-同源结构域转录因子，通过调节垂体激素的分泌来影响哺乳动物的体型。秋田,ShibaInu,和MameShibaInu狗是日本本土狗品种，具有不同的体型。为了确定Lhx3是否在这三个犬种的不同体型中起作用，我们对这三个品种的Lhx3基因进行了测序，这导致鉴定与体型相关的密码子280(S280N)中的SNP。该SNP的等位基因频率在大型秋田犬和两种较小的Shiba犬之间存在显着差异。为了验证这个SNP在身体大小上的功能，我们将这种改变引入小鼠的Lhx3基因中。与杂合突变体(S279N+/-)和野生型(S279N-/-)小鼠相比,发现纯合突变体小鼠(S279N+/+)在断奶几周后具有显著增加的体长和体重。这些结果表明，Lhx3中的非同义取代在调节哺乳动物的体型中起着重要作用。
