Gu Pengyu, Qi Xin, Zhou Yue, Wang Yun, Gao Xiang
Key Laboratory of Model Animal for Disease Study of Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing, China.
Genesis. 2012 May;50(5):429-36. doi: 10.1002/dvg.20815. Epub 2011 Dec 27.
Protein phosphatase 2A (PP2A) is one of the most abundant serine/threonine phosphatases, with a critical role in embryonic development and human disease. There are two isoforms of the catalytic subunit of PP2A, Ppp2ca and Ppp2cb. Null mutation of Ppp2ca leads to early embryonic lethality at E6.5, hindering functional study of PP2A beyond this stage. We generated conditional null alleles of Ppp2ca and Ppp2cb by flanking with loxP sites exons 3 to 5 of Ppp2ca and exon 3 of Ppp2cb. Ppp2ca(fl/fl) mice did not display any visible phenotype. Homozygous mutants in which Cre-mediated excision resulted in global deletion of Ppp2ca displayed embryonic lethality and developmental defects similar to those previously reported. Ppp2cb(Δ/Δ) mice generated by the same strategy did not display any obvious morphological or physiological defects. These mouse strains can serve as important genetic tools to study the roles of PP2A during development and disease in a spatial- or temporal-specific manner.
蛋白磷酸酶2A（PP2A）是最丰富的丝氨酸/苏氨酸磷酸酶之一，在胚胎发育和人类疾病中起关键作用。PP2A催化亚基有两种同工型，即Ppp2ca和Ppp2cb。Ppp2ca的无效突变导致在E6.5时胚胎早期致死，阻碍了在此阶段之后对PP2A的功能研究。我们通过在Ppp2ca的外显子3至5和Ppp2cb的外显子3两侧侧翼loxP位点，生成了Ppp2ca和Ppp2cb的条件性无效等位基因。Ppp2ca(fl/fl)小鼠未表现出任何可见的表型。Cre介导的切除导致Ppp2ca整体缺失的纯合突变体表现出胚胎致死性和发育缺陷，与先前报道的相似。通过相同策略产生的Ppp2cb(Δ/Δ)小鼠未表现出任何明显的形态或生理缺陷。这些小鼠品系可作为重要的遗传工具，以空间或时间特异性方式研究PP2A在发育和疾病中的作用。
