The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Metalloproteinase pregnancy-associated plasma protein A is a critical growth regulatory factor during fetal development
Abstract
Pregnancy-associated plasma protein A (PAPPA) is a metzincin superfamily metalloproteinase in the insulin-like growth factor (IGF) system. PAPPA increases IGF bioavailability and mitogenic effectiveness in vitro through regulated cleavage of IGF-binding protein 4 (IGFBP4). To determine its function in vivo, we generated PAPPA-null mice by gene targeting. Mice homozygous for targeted disruption of the PAPPA gene were viable but 60% the size of wild-type littermates at birth. The impact of the mutation was exerted during the early embryonic period prior to organogenesis, resulting in proportional dwarfism. PAPPA, IGF2 and IGFBP4 transcripts co-localized in wild-type embryos, and expression of IGF2 and IGFBP4 mRNA was not altered in PAPPA-deficient embryos. However,IGFBP4 proteolytic activity was completely lacking in fibroblasts derived from PAPPA-deficient embryos, and IGFBP4 effectively inhibited IGF-stimulated mitogenesis in these cells. These results provide the first direct evidence that PAPPA is an essential growth regulatory factor in vivo, and suggest a novel mechanism for regulated IGF bioavailability during early fetal development.
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Metadata
- Authors
- Conover, C. A., Bale, L. K., Overgaard, M. T., Johnstone, E. W., Laursen, U. H., Füchtbauer, E.-M., Oxvig, C., & van Deursen, J.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2004-03-01
- Volume
- 131
- Issue
- 5
- Pages
- 1187-1194
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2036997531
- Cited by
- 302
- References
- 35
- FWCI
- 9.54
- Type
- journal article
- Language
- en
- Open access
- closed
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