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Cited by 302

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

Conover, Cheryl A., Bale, Laurie K., Overgaard, Michael T., Johnstone, Edward W., Laursen, Ulla H., Füchtbauer, Ernst-Martin, Oxvig, Claus, van Deursen, Jan·2004·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
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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CoChat. (2026). Citation check: Metalloproteinase pregnancy-associated plasma protein A is a critical growth regulatory factor during fetal development. https://app.cochat.ai/papers/10.1242/dev.00997
The paper
Conover, C. A., Bale, L. K., Overgaard, M. T., Johnstone, E. W., Laursen, U. H., Füchtbauer, E.-M., Oxvig, C., & van Deursen, J. (2004). Metalloproteinase pregnancy-associated plasma protein A is a critical growth regulatory factor during fetal development. Development. https://doi.org/10.1242/dev.00997

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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