title: Hypothyroid phenotype of the Tpst2 mutant mouse is dependent upon genetic background.
abstract: 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.
authors.affiliation: Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Nishi 9, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Hosoda
authors.forename: Nobuya
authors.initials: N
authors.lastname: Sasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Agui
mesh_terms: D000818:Animals; D005260:Female; D007037:Hypothyroidism / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D017354:Point Mutation; D015238:Sulfotransferases / Q000235:genetics*
chemical_list: D015238:Sulfotransferases; C529648:TPST2 protein, mouse