Mice Deficient in both Pituitary Adenylyl Cyclase-activating Polypeptide and Vasoactive Intestinal Peptide Survive, but Display Growth Retardation and Sex-dependent Early Death

  • Pawel Niewiadomski
  • Anne-Claire Coûté-Monvoisin
  • Catalina Abad
  • Danny Ngo
  • Adrian Menezes
  • James A. Waschek
Article

Abstract

Pituitary adenylyl cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two closely related neuropeptides exhibiting overlapping activities which have actions on almost every organ system of the body. To determine if these peptides exert essential but redundant functions, we interbred VIP- and PACAP-deficient mice to obtain VIP/PACAP double knockout (DKO) mice. DKO mice had normal birth weights and survived to weaning, but exhibited a dramatic postnatal growth rate reduction. Analyses at postnatal day 16 indicated that all organs examined except the brain were reduced in mass by 40–70% compared to mixed background controls, with the thymus and spleen most profoundly affected. Brain size was also significantly reduced, but by only 10%. The reduced growth rate of DKO mice was associated with reduced serum concentrations of insulin-like growth hormone-1 (IGF-1), but unchanged levels of growth hormone. Despite the normal survival of DKO mice up to the weaning stage, many subsequently experienced early sudden death, with only 48% of females and 82% of males surviving past 6 months. The results indicate that a significant percentage of mice deficient in both VIP and PACAP survive to adulthood, but their growth rate is profoundly affected, and that females in particular exhibit high rate of mortality after about 3 months of age.

Keywords

Pituitary adenylyl cyclase-activating polypeptide PACAP Vasoactive intestinal peptide VIP Knockout Growth Postnatal Dwarf IGF-1 Growth hormone 

Notes

Acknowledgements

The present work was supported by the NIH grants CA110384, HD34475, HD04612, and HD06576.

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Copyright information

© Humana Press 2008

Authors and Affiliations

  • Pawel Niewiadomski
    • 1
  • Anne-Claire Coûté-Monvoisin
    • 1
  • Catalina Abad
    • 1
  • Danny Ngo
    • 1
  • Adrian Menezes
    • 1
  • James A. Waschek
    • 1
  1. 1.Semel Institute/Department of Psychiatry and Biobehavioral Research and Mental Retardation Research Center, David Geffen School of MedicineUniversity of California at Los AngelesLos AngelesUSA

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