Gamer Laura W, Tsuji Kunikazu, Cox Karen, Capelo Luciane P, Lowery Jonathan, Beppu Hideyuki, Rosen Vicki
Genesis. 2011 Sep;49(9):719-24. doi: 10.1002/dvg.20761. Epub 2011 Aug 19.
Initiation of BMP signaling is dependent upon activation of Type I BMP receptor by constitutively active Type II BMP receptor. Three Type II BMP receptors have been identified; Acvr2a and Acvr2b serve as receptors for BMPs and for activin-like ligands whereas BMPR-II functions only as a BMP receptor. As BMP signaling is required for endochondral ossification and loss of either Acvr2a or Acvr2b is not associated with deficits in limb development, we hypothesized that BMPR-II would be essential for BMP signaling during skeletogenesis. We removed BMPR-II from early limb mesoderm by crossing BMPR-II floxed mice with those carrying the Prx1-Cre transgene. Mice lacking limb expression of BMPR-II have normal skeletons that could not be distinguished from control littermates. From these data, we conclude that BMPR-II is not required for endochondral ossification in the limb where loss of BMPR-II may be compensated by BMP utilization of Acvr2a and Acvr2b.
骨形态发生蛋白(BMP)信号的起始依赖于组成型活性II型BMP受体对I型BMP受体的激活。已鉴定出三种II型BMP受体;激活素受体2A(Acvr2a)和激活素受体2B(Acvr2b)作为BMP和激活素样配体的受体,而骨形态发生蛋白受体II(BMPR-II)仅作为BMP受体发挥作用。由于软骨内成骨需要BMP信号,且Acvr2a或Acvr2b的缺失与肢体发育缺陷无关,我们推测BMPR-II在骨骼发生过程中对BMP信号至关重要。我们通过将BMPR-II基因敲除小鼠与携带Prx1-Cre转基因的小鼠杂交,从早期肢体中胚层去除BMPR-II。缺乏肢体BMPR-II表达的小鼠具有正常骨骼,与对照同窝小鼠无法区分。根据这些数据,我们得出结论,肢体软骨内成骨不需要BMPR-II,在肢体中BMPR-II的缺失可能通过Acvr2a和Acvr2b对BMP的利用得到补偿。