DEVELOPMENT OF VIABLE CALCIUM RECEPTOR KNOCKOUT MICE

本研究的总体目标是阐明细胞外钙敏感受体基因(CAR)在许多组织中表达的各种功能。由于甲状旁腺功能亢进和严重的高钙血症，CAR基因零突变纯合的小鼠在出生后20天内死亡。这项研究提案的具体目标是开发一种健康的小鼠模型，该模型对CAR基因的零突变是纯合子的。已知这些小鼠的高钙血症至少部分是由于这些小鼠不能适当地调节甲状旁腺分泌的甲状旁腺激素(PTH)。因此，假设将含有CAR的转基因靶向表达到甲状旁腺将足以维持在所有其他组织中缺乏CAR的小鼠的甲状旁腺激素和钙水平，从而使它们免于早期死亡。

The overall goal of this research is to elucidate the various functions of the extracellular calcium sensing receptor gene (CaR) in the many tissues in which it is expressed. Mice that are homozygous for a null mutation of the CaR gene die within 20 days of birth due to hyperparathyroidism and severe hypercalcemia. The specific goal of this research proposal is to develop a healthy mouse model that is homozygous for a null mutation of the CaR gene. The hypercalcemia in these mice is known to be due, at least in part, to the inability of these mice to properly regulate parathyroid hormone (PTH) secretion from the parathyroid gland. Therefore, it is hypothesized that targeted expression of a transgene containing the CaR to the parathyroid gland will be sufficient to maintain proper PTH and calcium levels in mice lacking CaR expression in all other tissues and thus rescue them from early death.