Pregnancy-Associated Plasma Protein-A2 (PAPP-A2): Tissue Expression and Biological Consequences of Gene Knockout in Mice
Pregnancy-Associated Plasma Protein-A2 (PAPP-A2): Tissue Expression and Biological Consequences of Gene Knockout in Mice
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DOI：
10.1210/en.2011-0036
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发表时间：
2011-07-01
期刊：
影响因子：
4.8
通讯作者：
Powell, David R.
中科院分区：
文献类型：
--
作者：
Conover, Cheryl A.;Boldt, Henning B.;Powell, David R.
妊娠相关血浆蛋白-A2(PAPP-A2)是梅津星超家族中PAPP-A的新同源物。然而，与积累的关于PAPP-A的数据相比，人们对PAPP-A2的了解很少。在本研究中，我们测定了野生型(WT)小鼠PAPP-A2基因的组织表达模式，并表征了PAPP-A2全局性缺陷小鼠的表型。在WT小鼠中，表达PAPP-A2的组织比表达PAPP-A的组织更有限。PAPP-A2在胎盘中的表达最高，在胎儿、骨骼和生殖组织中也有大量表达。杂合育种产生了预期的Pappa2基因孟德尔分布和出生时正常大小的存活纯合子PAPP-A2基因敲除(KO)小鼠。PAPP-A2 KO小鼠最显著的表型是出生后生长迟缓。雄性和雌性PAPP-A2 KO小鼠的体重分别比WT窝小鼠轻10%和25%-30%。PAPP-A2 KO小鼠的成年股骨和身体长度也减少了，但对骨密度没有显著影响。PAPP-A2 KO小鼠是有生育能力的，但生殖力受损。PAPP-A的表达没有改变以补偿PAPP-A2表达的丧失，PAPP-A2‘S的主要底物胰岛素样生长因子结合蛋白-5的蛋白降解也没有改变。总之，KO基因的组织表达模式和生物学后果表明，PAPP-A2和PAPP-A在小鼠中具有不同的生理作用。(内分泌学152：2837-2844,2011)
Pregnancy-associated plasma protein-A2 (PAPP-A2) is a novel homolog of PAPP-A in the metzincin superfamily. However, compared with the accumulating data on PAPP-A, very little is known about PAPP-A2. In this study, we determined the tissue expression pattern of PAPP-A2 mRNA in wild-type (WT) mice and characterized the phenotype of mice with global PAPP-A2 deficiency. Tissues expressing PAPP-A2 in WT mice were more limited than those expressing PAPP-A. The highest PAPP-A2 mRNA expression was found in the placenta, with abundant expression in fetal, skeletal, and reproductive tissues. Heterozygous breeding produced the expected Mendelian distribution for the pappa2 gene and viable homozygous PAPP-A2 knockout (KO) mice that were normal size at birth. The most striking phenotype of the PAPP-A2 KO mouse was postnatal growth retardation. Male and female PAPP-A2 KO mice had 10 and 25-30% lower body weight, respectively, than WT littermates. Adult femur and body length were also reduced in PAPP-A2 KO mice, but without significant effects on bone mineral density. PAPP-A2 KO mice were fertile, but with compromised fecundity. PAPP-A expression was not altered to compensate for the loss of PAPP-A2 expression, and proteolysis of PAPP-A2's primary substrate, IGF-binding protein-5, was not altered in fibroblasts from PAPP-A2 KO embryos. In conclusion, tissue expression patterns and biological consequences of gene KO indicate distinct physiological roles for PAPP-A2 and PAPP-A in mice. (Endocrinology 152: 2837-2844, 2011)