Congenital hypothyroidism (cretinism) in neuroD2-deficient mice.
Mice lacking neuroD2, a basic helix-loop-helix transcription factor involved in brain development, show growth retardation and other abnormalities consistent with hypothalamic-pituitary-thyroid (HPT) axis dysfunction. neuroD2 is expressed in the paraventricular hypothalamic nuclei, the anterior lobe of pituitary, and the thyroid gland. In neuroD2-deficient mice, thyrotropin-releasing hormone, thyroid-stimulating hormone, and thyroid hormone are decreased in these three regions, respectively. neuroD2-null mice typically die 2 to 3 weeks after birth, but those treated with replacement doses of thyroxine survived more than 8 weeks. These data indicate that neuroD2 is expressed throughout the HPT axis and that all levels of the axis are functionally affected by its absence in mice.
Lin
Chin-Hsing
CH
Clinical Research, Fred Hutchinson Cancer Research Center, Mailstop D4-100, 1100 Fairview Ave. N., Seattle, WA 98109, USA.
Tapscott
Stephen J
SJ
Olson
James M
JM
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D003409:Congenital Hypothyroidism / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009479:Neuropeptides / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; C098995:Neurod2 protein, mouse