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Pregnancy-associated plasma protein-A2 (PAPP-A2): tissue expression and biological consequences of gene knockout in mice.
- Source :
-
Endocrinology [Endocrinology] 2011 Jul; Vol. 152 (7), pp. 2837-44. Date of Electronic Publication: 2011 May 17. - Publication Year :
- 2011
-
Abstract
- 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.
- Subjects :
- Animals
Body Weight
Bone Development
Cells, Cultured
Embryo, Mammalian cytology
Embryo, Mammalian metabolism
Female
Heterozygote
Hydrolysis
Infertility genetics
Insulin-Like Growth Factor Binding Protein 5 metabolism
Isoenzymes genetics
Isoenzymes physiology
Male
Metalloendopeptidases genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Organ Specificity
Pregnancy
RNA, Messenger metabolism
Sex Characteristics
Gene Expression
Metalloendopeptidases physiology
Pregnancy-Associated Plasma Protein-A genetics
Pregnancy-Associated Plasma Protein-A metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7170
- Volume :
- 152
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 21586553
- Full Text :
- https://doi.org/10.1210/en.2011-0036