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Metalloproteinase pregnancy-associated plasma protein A is a critical growth regulatory factor during fetal

Cheryl A Conover1, Laurie K Bale, Michael T Overgaard

  • 1The Division of Endocrinology, Metabolism and Nutrition, Endocrine Research Unit, Mayo Clinic and Mayo Foundation, 200 First Street SW, Rochester, MN 55905, USA. conover.cheryl@mayo.edu

Development (Cambridge, England)
|February 20, 2004
PubMed

Insights

Pregnancy-associated plasma protein A (PAPPA) is crucial for fetal growth. PAPPA deficiency in mice leads to proportional dwarfism, highlighting its essential role in regulating growth factors during early development.

Area of Science:

  • Biochemistry
  • Developmental Biology
  • Genetics

Background:

  • Pregnancy-associated plasma protein A (PAPPA) is a metalloproteinase within the insulin-like growth factor (IGF) system.
  • PAPPA enhances IGF bioavailability and activity by cleaving IGF-binding protein 4 (IGFBP4) in vitro.

Purpose of the Study:

  • To investigate the in vivo function of PAPPA in embryonic and fetal development.
  • To determine the role of PAPPA in regulating IGF bioavailability and growth.

Main Methods:

  • Generation of PAPPA-null mice using gene targeting.
  • Analysis of embryonic size, organogenesis, and transcript localization (PAPPA, IGF2, IGFBP4).
  • Assessment of IGFBP4 proteolytic activity and IGF-stimulated mitogenesis in PAPPA-deficient fibroblasts.

Main Results:

  • PAPPA-null mice exhibited proportional dwarfism, being 60% smaller than wild-type littermates at birth.
  • The growth impact occurred during early embryogenesis, prior to organogenesis.
  • IGFBP4 proteolytic activity was absent in PAPPA-deficient cells, and IGFBP4 inhibited IGF-stimulated mitogenesis.

Conclusions:

  • PAPPA is an essential growth regulatory factor in vivo.
  • PAPPA plays a critical role in regulating IGF bioavailability during early fetal development.
  • This study reveals a novel mechanism for growth factor regulation in embryonic development.

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