Mice deficient in both pituitary adenylyl cyclase-activating polypeptide and vasoactive intestinal peptide survive, but display growth retardation and sex-dependent early death.
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.
Niewiadomski
Pawel
P
Semel Institute/Department of Psychiatry and Biobehavioral Research and Mental Retardation Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Coûté-Monvoisin
Anne-Claire
AC
Abad
Catalina
C
Ngo
Danny
D
Menezes
Adrian
A
Waschek
James A
JA
D000818:Animals; D005260:Female; D006130:Growth Disorders / Q000235:genetics* / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000002:abnormalities; D010641:Phenotype; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism; D015996:Survival Rate; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D013002:Somatomedins; D014660:Vasoactive Intestinal Peptide; D013006:Growth Hormone