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.
Stazione Zoologica Anton Dohrn, Villa Comunale I, Naples 80121, Italy.
Elena
E
Amendola
Remo
R
Sanges
Antonella
A
Galvan
Nina
N
Dathan
Giacomo
G
Manenti
Giuseppe
G
Ferrandino
Francesca Maria
FM
Alvino
Tina
T
Di Palma
Marzia
M
Scarfò
Mariastella
M
Zannini
Tommaso A
TA
Dragani
Mario
M
De Felice
Roberto
R
Di Lauro
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