Ma Lijiang, Martin James F
Alkek Institute of Biosciences and Technology, Texas A&M System Health Science Center, Houston, TX 77030, USA.
Genesis. 2005 Jul;42(3):203-6. doi: 10.1002/gene.20132.
Bone morphogenetic proteins (Bmp's) are known to play many important roles in embryogenesis. In addition, recent data from human genetic studies has revealed that Bmp's also have important functions in maintenance of the adult phenotype and aging. The original Bmp2 germline null allele resulted in lethality at embryonic day 7.0-10.5 due to malformation of the amnion/chorion and cardiac malformations. Because the early embryonic lethality of the Bmp2 germline null allele hinders further investigation into Bmp2 function at later stages, we generated a Bmp2 conditional null allele. Using gene targeting in mouse embryonic stem (ES) cells, we introduced LoxP sites upstream and downstream of Bmp2 exon 3 that encodes the mature peptide. Our results indicate that the Bmp2 conditional null allele is a true conditional null that encodes wildtype activity and reverts to a null allele after cre recombinase-induced recombination.
骨形态发生蛋白(Bmp)在胚胎发育中发挥着许多重要作用。此外,来自人类遗传学研究的最新数据表明,Bmp在维持成体表型和衰老过程中也具有重要功能。最初的Bmp2种系无效等位基因由于羊膜/绒毛膜畸形和心脏畸形,在胚胎第7.0 - 10.5天导致死亡。由于Bmp2种系无效等位基因的早期胚胎致死性阻碍了对Bmp2在后期功能的进一步研究,我们构建了一个Bmp2条件性无效等位基因。利用小鼠胚胎干细胞(ES)中的基因靶向技术,我们在编码成熟肽的Bmp2外显子3的上游和下游引入了LoxP位点。我们的结果表明,Bmp2条件性无效等位基因是一个真正的条件性无效基因,它编码野生型活性,并在cre重组酶诱导的重组后恢复为无效等位基因。