A Locus on Mouse Chromosome 2 Is Involved in Susceptibility to Congenital Hypothyroidism and Contains an Essential Gene Expressed in Thyroid

被引：17

作者：

Amendola, Elena ^{[1
,7
]}

Sanges, Remo ^{[1
]}

Galvan, Antonella ^{[2
]}

Dathan, Nina ^{[6
]}

Manenti, Giacomo ^{[2
]}

Ferrandino, Giuseppe ^{[3
]}

Alvino, Francesca Maria ^{[1
]}

Di Palma, Tina ^{[2
,5
]}

Scarfo, Marzia ^{[1
]}

Zannini, Mariastella ^{[5
]}

Dragani, Tommaso A.

De Felice, Mario ^{[1
,4
]}

Di Lauro, Roberto ^{[1
,4
,7
]}

机构：

[1] Biogem, I-83031 Ariano Irpino, AV, Italy

[2] Ist Nazl Tumori, Fdn IRCSS, Dipartimento Oncol Sperimentale & Med Mol, I-20133 Milan, Italy

[3] Biogem SCRL, Inst Genet Res Gaetano Salvatore IRGS, I-83031 Ariano Irpino, Italy

[4] Univ Naples Federico 2, Dipartimento Biol & Patol Cellulare & Mol, I-80131 Naples, Italy

[5] CNR, Ist Endocrinol & Oncol Sperimentale, I-80131 Naples, Italy

[6] CNR, Ist Biostrutture & Bioimmagini, I-80131 Naples, Italy

[7] Stn Zool A Dohrn, I-80121 Naples, Italy

来源：

ENDOCRINOLOGY | 2010年 / 151卷 / 04期

关键词：

QUANTITATIVE TRAIT LOCI; OF-FUNCTION MUTATION; PHENOTYPIC VARIABILITY; MISSENSE MUTATION; HOMEOBOX GENE; DYSGENESIS; TRANSCRIPTION; PAX8; MICE; PROTEIN;

D O I：

10.1210/en.2009-1240

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (Endocrinology 151: 1948-1958, 2010)

引用

页码：1948 / 1958

页数：11

共 51 条

[1] The nature and identification of quantitative trait loci: a community's view [J].

Abiola, O ;

Angel, JM ;

Avner, P ;

Bachmanov, AA ;

Belknap, JK ;

Bennett, B ;

Blankenhorn, EP ;

Blizard, DA ;

Bolivar, V ;

Brockmann, GA ;

Buck, KJ ;

Bureau, JF ;

Casley, WL ;

Chesler, EJ ;

Cheverud, JM ;

Churchill, GA ;

Cook, M ;

Crabbe, JC ;

Crusio, WE ;

Darvasi, A ;

de Haan, G ;

Demant, P ;

Doerge, RW ;

Elliott, RW ;

Farber, CR ;

Flaherty, L ;

Flint, J ;

Gershenfeld, H ;

Gu, JPGJ ;

Gu, WK ;

Himmelbauer, H ;

Hitzemann, R ;

Hsu, HC ;

Hunter, K ;

Iraqi, FA ;

Jansen, RC ;

Johnson, TE ;

Jones, BC ;

Kempermann, G ;

Lammert, F ;

Lu, L ;

Manly, KF ;

Matthews, DB ;

Medrano, JF ;

Mehrabian, M ;

Mittleman, G ;

Mock, BA ;

Mogil, JS ;

Montagutelli, X ;

Morahan, G .

NATURE REVIEWS GENETICS, 2003, 4 (11) :911-916

[2] Identification of interactive loci linked to insulin and leptin in mice with genetic insulin resistance [J].

Almind, K ;

Kulkarni, RN ;

Lannon, SM ;

Kahn, CR .

DIABETES, 2003, 52 (06) :1535-1543

[3] A mouse model demonstrates a multigenic origin of congenital hypothyroidism [J].

Amendola, E ;

De Luca, P ;

Macchia, PE ;

Terracciano, D ;

Rosica, A ;

Chiappetta, G ;

Kimura, S ;

Mansouri, A ;

Affuso, A ;

Arra, C ;

Macchia, V ;

Di Lauro, R ;

De Felice, M .

ENDOCRINOLOGY, 2005, 146 (12) :5038-5047

[4] A novel missense mutation in human TTF-2 (FKHL15) gene associated with congenital hypothyroidism but not athyreosis [J].

Baris, I. ;

Arisoy, A. E. ;

Smith, A. ;

Agostini, M. ;

Mitchell, C. S. ;

Park, S. M. ;

Halefoglu, A. M. ;

Zengin, E. ;

Chatterjee, V. K. ;

Battaloglu, E. .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2006, 91 (10) :4183-4187

[5] Cardiac septal and valvular dysmorphogenesis in mice heterozygous for mutations in the homeobox gene Nkx2-5 [J].

Biben, C ;

Weber, R ;

Kesteven, S ;

Stanley, E ;

McDonald, L ;

Elliott, DA ;

Barnett, L ;

Köentgen, F ;

Robb, L ;

Feneley, M ;

Harvey, RP .

CIRCULATION RESEARCH, 2000, 87 (10) :888-895

[6] Sequence and structure-based prediction of eukaryotic protein phosphorylation sites [J].

Blom, N ;

Gammeltoft, S ;

Brunak, S .

JOURNAL OF MOLECULAR BIOLOGY, 1999, 294 (05) :1351-1362

[7] R/qtl: QTL mapping in experimental crosses [J].

Broman, KW ;

Wu, H ;

Sen, S ;

Churchill, GA .

BIOINFORMATICS, 2003, 19 (07) :889-890

[8] Development of a novel polygenic model of NIDDM in mice heterozygous for IR and IRS-1 null alleles [J].

Bruning, JC ;

Winnay, J ;

BonnerWeir, S ;

Taylor, SI ;

Accili, D ;

Kahn, CR .

CELL, 1997, 88 (04) :561-572

[9] Epistasis:: too often neglected in complex trait studies? [J].

Carlborg, Ö ;

Haley, CS .

NATURE REVIEWS GENETICS, 2004, 5 (08) :618-U4

[10] Linkage and mutational analysis of familial thyroid dysgenesis demonstrate genetic heterogeneity implicating novel genes [J].

Castanet, M ;

Sura-Trueba, S ;

Chauty, A ;

Carré, A ;

de Roux, N ;

Heath, S ;

Léger, J ;

Lyonnet, S ;

Czernichow, P ;

Polak, M .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2005, 13 (02) :232-239

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