Perturbed thyroid morphology and transient hypothyroidism symptoms in Hoxa5 mutant mice.
The Hox family of transcriptional regulators has been extensively studied for their role in axial and appendicular patterning. Genetic analyses have also unveiled Hox gene function in organogenesis and postnatal development. A phenotypical survey of the Hoxa5(-/-) mutant mice shows that the surviving mutants display symptoms of hypothyroidism, including transient growth retardation, and delayed eye opening and ear elevation. Thyroid gland morphogenesis initiates normally, but follicle formation and thyroglobulin processing are abnormal at late gestation. The expression of several molecular markers essential for thyroid gland formation and function, namely Nkx2.1, Pax8, and Titf2, is affected in the developing thyroid gland of Hoxa5(-/-) mutants. As a consequence, the expression of thyroid effector genes, including the thyroglobulin and thyroperoxidase genes, is perturbed. Our characterization reveals that the loss of Hoxa5 function transiently affects thyroid development in a non-cell autonomous manner.
Meunier
Dominique
D
Centre de recherche en cancérologie de l'Université Laval, Centre Hospitalier Universitaire de Québec, L'Hôtel-Dieu de Québec, Québec, Canada.
Aubin
Josée
J
Jeannotte
Lucie
L
D000818:Animals; D019521:Body Patterning; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D007037:Hypothyroidism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D010641:Phenotype; D010750:Phosphoproteins; D013954:Thyroglobulin / Q000096:biosynthesis; D013961:Thyroid Gland / Q000196:embryology / Q000378:metabolism* / Q000473:pathology*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C472789:Foxe1 protein, mouse; C489213:HOXA5 protein, human; D018398:Homeodomain Proteins; C059637:Hoxa5 protein, mouse; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C499496:Pax8 protein, mouse; D010750:Phosphoproteins; D015534:Trans-Activators; D014157:Transcription Factors; D013972:Thyrotropin; D013954:Thyroglobulin; D013974:Thyroxine