TY - JOUR
T1 - Genetic ablation of parathyroid glands reveals another source of parathyroid hormone
AU - Günther, Thomas
AU - Chen, Zhou Feng
AU - Kim, Jaesang
AU - Priemel, Matthias
AU - Rueger, Johannes M.
AU - Amling, Michael
AU - Moseley, Jane M.
AU - Martin, T. John
AU - Anderson, David J.
AU - Karsenty, Gerard
PY - 2000/7/13
Y1 - 2000/7/13
N2 - The parathyroid glands are the only known source of circulating parathyroid hormone (PTH), which initiates an endocrine cascade that regulates serum calcium concentration. Glial cells missing2 (Gcm2), a mouse homologue of Drosophila Gcm, is the only transcription factor whose expression is restricted to the parathyroid glands. Here we show that Gcm2- deficient mice lack parathyroid glands and exhibit a biological hypoparathyroidism, identifying Gcm2 as a master regulatory gene of parathyroid gland development. Unlike PTH receptor-deficient mice, however, Gcm2-deficient mice are viable and fertile, and have only a mildly abnormal bone phenotype. Despite their lack of parathyroid glands, Gcm2-deficient mice have PTH serum levels identical to those of wild-type mice, as do parathyroidectomized wild-type animals. Expression and ablation studies identified the thymus, where Gcm1, another Gcm homologue, is expressed, as the additional, downregulatable source of PTH. Thus, Gcm2 deletion uncovers an auxiliary mechanism for the regulation of calcium homeostasis in the absence of parathyroid glands. We propose that tiffs backup mechanism may be a general feature of endocrine regulation.
AB - The parathyroid glands are the only known source of circulating parathyroid hormone (PTH), which initiates an endocrine cascade that regulates serum calcium concentration. Glial cells missing2 (Gcm2), a mouse homologue of Drosophila Gcm, is the only transcription factor whose expression is restricted to the parathyroid glands. Here we show that Gcm2- deficient mice lack parathyroid glands and exhibit a biological hypoparathyroidism, identifying Gcm2 as a master regulatory gene of parathyroid gland development. Unlike PTH receptor-deficient mice, however, Gcm2-deficient mice are viable and fertile, and have only a mildly abnormal bone phenotype. Despite their lack of parathyroid glands, Gcm2-deficient mice have PTH serum levels identical to those of wild-type mice, as do parathyroidectomized wild-type animals. Expression and ablation studies identified the thymus, where Gcm1, another Gcm homologue, is expressed, as the additional, downregulatable source of PTH. Thus, Gcm2 deletion uncovers an auxiliary mechanism for the regulation of calcium homeostasis in the absence of parathyroid glands. We propose that tiffs backup mechanism may be a general feature of endocrine regulation.
UR - http://www.scopus.com/inward/record.url?scp=0034644149&partnerID=8YFLogxK
U2 - 10.1038/35018111
DO - 10.1038/35018111
M3 - Article
C2 - 10910362
AN - SCOPUS:0034644149
SN - 0028-0836
VL - 406
SP - 199
EP - 203
JO - Nature
JF - Nature
IS - 6792
ER -