論文

査読有り
2012年1月

Identifying Quantitative Trait Loci Affecting Resistance to Congenital Hypothyroidism in 129(+Ter)/SvJcl Strain Mice

PLOS ONE
  • Yayoi Hosoda
  • ,
  • Nobuya Sasaki
  • ,
  • Yayoi Kameda
  • ,
  • Daisuke Torigoe
  • ,
  • Takashi Agui

7
1
開始ページ
e31035
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0031035
出版者・発行元
PUBLIC LIBRARY SCIENCE

Tyrosylprotein sulfotransferase 2 (TPST2) is one of the enzymes responsible for tyrosine O-sulfation and catalyzes the sulfation of the specific tyrosine residue of thyroid stimulating hormone receptor (TSHR). Since this modification is indispensable for the activation of TSH signaling, a non-functional TPST2 mutation (Tpst2(grt)) in DW/J-grt mice leads to congenital hypothyroidism (CH) characterized by severe thyroid hypoplasia and dwarfism related to TSH hyporesponsiveness. Previous studies indicated that the genetic background of the 129(+Ter)/SvJcl (129) mouse strain ameliorates Tpst2(grt)-induced CH. To identify loci responsible for CH resistance in 129 mice, we performed quantitative trait locus (QTL) analysis using backcross progenies from susceptible DW/J and resistant 129 mice. We used the first principal component calculated from body weights at 5, 8 and 10 weeks as an indicator of CH, and QTL analysis mapped a major QTL showing a highly significant linkage to the distal portion of chromosome (Chr) 2; between D2Mit62 and D2Mit304, particularly close to D2Mit255. In addition, two male-specific QTLs showing statistically suggestive linkage were also detected on Chrs 4 and 18, respectively. All QTL alleles derived from the 129 strain increased resistance to growth retardation. There was also a positive correlation between recovery from thyroid hypoplasia and the presence of the 129 allele at D2Mit255 in male progenies. These results suggested that the major QTL on Chr 2 is involved in thyroid development. Moreover, since DW/J congenic strain mice carrying both a Tpst2(grt) mutation and 129 alleles in the major QTL show resistance to dwarfism and thyroid hypoplasia, we confirmed the presence of the resistant gene in this region, and that it is involved in thyroid development. Further genetical analysis should lead to identification of genes for CH tolerance and, from a better understanding of thyroid organogenesis and function, the subsequent development of new treatments for thyroid disorders.

Web of Science ® 被引用回数 : 4

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0031035
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/22299049
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000301704200056&DestApp=WOS_CPL
ID情報
  • DOI : 10.1371/journal.pone.0031035
  • ISSN : 1932-6203
  • PubMed ID : 22299049
  • Web of Science ID : WOS:000301704200056

エクスポート
BibTeX RIS