TARGETED DISRUPTION OF THE MOUSE CALCITONIN GENE

尽管已知降钙素（CT）是药理学抑制剂， 骨吸收和降钙素基因相关产物（CGRP）是一种有效的 血管扩张剂和神经肽，这些相关的生理作用， 肽仍然未经证实。CALC I和CALC II基因编码CGRP。 CALC I的转录导致编码CT和CGRP-1的mRNA。 CALC II仅产生CGRP（CGRP-II）。这两种CGRP肽是高度 同源的，具有独特的，有时重叠的组织分布。 到 剖析这些密切相关的激素对正常的 哺乳动物发育和生理学，动物模型， 将产生每个基因座处的突变。 为了实现这一点，每个基因 利用靶向基因治疗技术， 多能小鼠胚胎干细胞（ES细胞）中的破坏。

Although it is known that calcitonin (CT) is a pharmacological inhibitor of bone resorption and calcitonin gene-related product (CGRP) is a potent vasodilator and neuropeptide, the physiologic role for these related peptides remains unproved. The CALC I and CALC II genes encode for CGRP. Transcription of CALC I results in an mRNA coding for both CT and CGRP-I. CALC II produces only CGRP (CGRP-II). The two CGRP peptides are highly homologous with unique, at times overlapping, tissue distributions. To dissect the contributions of these closely related hormones to normal mammalian development and physiology, animal models containing null mutations at each locus will be generated. To accomplish this, each gene will be selectively eliminated using the technique of targeted gene disruption in pluripotent mouse embryonic stem (ES) cells.