Hypothyroid phenotype of the Tpst2 mutant mouse is dependent upon genetic background
Hypothyroid phenotype of the Tpst2 mutant mouse is dependent upon genetic background
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DOI：
10.2220/biomedres.31.207
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发表时间：
2010-06-01
影响因子：
1.2
通讯作者：
Agui, Takashi
中科院分区：
文献类型：
--
作者：
Hosoda, Yayoi;Sasaki, Nobuya;Agui, Takashi
DW/J-grt是一种先天性甲状腺功能减退小鼠模型，其特征为生长迟缓、T3和T4水平显著降低以及与TSH低反应性相关的重度甲状腺发育不全。以前，我们确定了DW/J-grt小鼠中Tpst 2基因的点突变，导致酶活性降低，并证明了Tpst 2转基因在体外和体内都挽救了突变表型。甲状腺功能减退症的严重程度是高度可变的，表明人类中修饰基因的影响。在这项研究中，为了鉴定甲状腺功能减退症的修饰基因/抗性基因，我们在C57 BL/6 J和129/SvJcl（129）遗传背景上产生了携带这种Tpst 2（grt）突变的同源株，并分析了生长速度和甲状腺功能。有趣的是，129只同类小鼠表现出正常的生长和甲状腺功能。结果表明，129株具有减轻甲减的修饰基因。因此，129只小鼠修饰位点的鉴定将为先天性甲状腺功能减退症相关基因的研究提供重要的新信息。
DW/J-grt is a congenital hypothyroid mouse model that is characterized by growth retardation, significantly lowered T3 and T4 levels, and severe thyroid hypoplasia related to TSH hyporesponsiveness. Previously, we identified the point mutation of the Tpst2 gene in DW/J-grt mice that causes a decrease in the enzymatic activity, and demonstrated that the Tpst2 transgene rescues the mutant phenotypes both in vitro and in vivo. The severity of hypothyroidism is highly variable indicating the influence of modifier genes in humans. In this study, to identify the modifier/resistant gene(s) to hypothyroidism, we produced congenic strains carrying this Tpst2(grt) mutation on the C57BL/6J and 129/SvJcl (129) genetic backgrounds and analyzed growth rate and thyroid function. Interestingly, the 129 congenic mice exhibited normal growth and thyroid function. The result suggests that 129 strain has the modifier(s) of attenuation of hypothyroidism. Therefore, the identification of the modifier loci of 129 mice will provide important new information about the gene(s) related to congenital hypothyroidism.