Otto F, Thornell A P, Crompton T, Denzel A, Gilmour K C, Rosewell I R, Stamp G W, Beddington R S, Mundlos S, Olsen B R, Selby P B, Owen M J
Imperial Cancer Research Fund, Lincoln's Inn Fields, London, United Kingdom.
Cell. 1997 May 30;89(5):765-71. doi: 10.1016/s0092-8674(00)80259-7.
We have generated Cbfa1-deficient mice. Homozygous mutants die of respiratory failure shortly after birth. Analysis of their skeletons revealed an absence of osteoblasts and bone. Heterozygous mice showed specific skeletal abnormalities that are characteristic of the human heritable skeletal disorder, cleidocranial dysplasia (CCD). These defects are also observed in a mouse Ccd mutant for this disease. The Cbfa1 gene was shown to be deleted in the Ccd mutation. Analysis of embryonic Cbfa1 expression using a lacZ reporter gene revealed strong expression at sites of bone formation prior to the earliest stages of ossification. Thus, the Cbfa1 gene is essential for osteoblast differentiation and bone formation, and the Cbfa1 heterozygous mouse is a paradigm for a human skeletal disorder.
我们培育出了Cbfa1基因缺失的小鼠。纯合突变体在出生后不久死于呼吸衰竭。对其骨骼的分析显示，成骨细胞和骨骼缺失。杂合小鼠表现出特定的骨骼异常，这些异常是人类遗传性骨骼疾病锁骨颅骨发育不全（CCD）的特征。在该疾病的小鼠Ccd突变体中也观察到了这些缺陷。结果表明，Cbfa1基因在Ccd突变中被删除。利用lacZ报告基因对胚胎Cbfa1表达进行分析，发现在骨化最早阶段之前的骨形成部位有强表达。因此，Cbfa1基因对成骨细胞分化和骨形成至关重要，Cbfa1杂合小鼠是人类骨骼疾病的一个范例。
