A locus on mouse chromosome 2 is involved in susceptibility to congenital hypothyroidism and contains an essential gene expressed in thyroid.
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.
Amendola
Elena
E
Stazione Zoologica Anton Dohrn, Villa Comunale I, Naples 80121, Italy.
Sanges
Remo
R
Galvan
Antonella
A
Dathan
Nina
N
Manenti
Giacomo
G
Ferrandino
Giuseppe
G
Alvino
Francesca Maria
FM
Di Palma
Tina
T
Scarfò
Marzia
M
Zannini
Mariastella
M
Dragani
Tommaso A
TA
De Felice
Mario
M
Di Lauro
Roberto
R
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics; D003409:Congenital Hypothyroidism / Q000235:genetics* / Q000378:metabolism; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000002:abnormalities* / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood
D050956:HSP40 Heat-Shock Proteins; D013972:Thyrotropin