We report here the mapping of a chromosomal region responsible for strain-specific development of congenital hypothyroidism in mice heterozygous for null mutations in genes encoding Nkx2-1/Titf1 and Pax8. The two strains showing a differential predisposition to congenital hypothyroidism contain several single-nucleotide polymorphisms in this locus, one of which leads to a nonsynonymous amino acid change in a highly conserved region of Dnajc17, a member of the type III heat-shock protein-40 (Hsp40) family. We demonstrate that Dnajc17 is highly expressed in the thyroid bud and had an essential function in development, suggesting an important role of this protein in organogenesis and/or function of the thyroid gland. Copyright © 2010 by The Endocrine Society.
A Locus on Mouse Chromosome 2 Is Involved in Susceptibility to Congenital Hypothyroidism and Contains an Essential Gene Expressed in Thyroid / Amendola, Elena; Sanges, Remo; Galvan, Antonella; Dathan, Nina; Manenti, Giacomo; Ferrandino, Giuseppe; Alvino, Francesca Maria; Di Palma, Tina; Scarfò, Marzia; Zannini, Mariastella; Dragani, Tommaso A.; De Felice, Mario; Di Lauro, Roberto. - In: ENDOCRINOLOGY. - ISSN 0013-7227. - 151:4(2010), pp. 1948-1958. [10.1210/en.2009-1240]
A Locus on Mouse Chromosome 2 Is Involved in Susceptibility to Congenital Hypothyroidism and Contains an Essential Gene Expressed in Thyroid
Amendola, Elena;Alvino, Francesca Maria;De Felice, Mario;Di Lauro, Roberto
2010
Abstract
We report here the mapping of a chromosomal region responsible for strain-specific development of congenital hypothyroidism in mice heterozygous for null mutations in genes encoding Nkx2-1/Titf1 and Pax8. The two strains showing a differential predisposition to congenital hypothyroidism contain several single-nucleotide polymorphisms in this locus, one of which leads to a nonsynonymous amino acid change in a highly conserved region of Dnajc17, a member of the type III heat-shock protein-40 (Hsp40) family. We demonstrate that Dnajc17 is highly expressed in the thyroid bud and had an essential function in development, suggesting an important role of this protein in organogenesis and/or function of the thyroid gland. Copyright © 2010 by The Endocrine Society.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
