title: Pregnancy-associated plasma protein-A2 (PAPP-A2): tissue expression and biological consequences of gene knockout in mice.
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.
authors.affiliation: Endocrine Research Unit, Division of Endocrinology, Metabolism, and Nutrition, College of Medicine Mayo Clinic, 200 First Street SW, 5-194 Joseph, Rochester, Minnesota 55905, USA. Conover.Cheryl@mayo.edu
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Conover
authors.forename: Henning B
authors.initials: HB
authors.lastname: Boldt
authors.forename: Laurie K
authors.initials: LK
authors.lastname: Bale
authors.forename: Kari B
authors.initials: KB
authors.lastname: Clifton
authors.forename: Jacquelyn A
authors.initials: JA
authors.lastname: Grell
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Mader
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Mason
authors.forename: David R
authors.initials: DR
authors.lastname: Powell
mesh_terms: D000818:Animals; D001835:Body Weight; D001846:Bone Development; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006579:Heterozygote; D006868:Hydrolysis; D007246:Infertility / Q000235:genetics; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012727:Sex Characteristics
chemical_list: D018975:Insulin-Like Growth Factor Binding Protein 5; D007527:Isoenzymes; D012333:RNA, Messenger; D008666:Metalloendopeptidases; C514948:PAPPA2 protein, mouse; D011266:Pregnancy-Associated Plasma Protein-A