Overexpression of PACAP in the pancreas failed to rescue early postnatal mortality in PACAP-null mice.
PACAP exerts multiple activities as a hormone and neurotransmitter, and has been proposed to play vital roles in a variety of neuronal functions. PACAP is also involved in insulin secretion from pancreatic beta-cells. Recently, we and other groups demonstrated that PACAP-deficient mice (PACAP(-/-)) are viable, but suffer from increased postnatal mortality. To ascertain whether this high mortality is rescued by overexpression of PACAP in peripheral tissue (such as pancreas), we performed a genetic cross between PACAP(-/-) and our recently developed transgenic mice overexpressing PACAP in pancreatic beta-cells; and then examined the survival rate of their F2 progeny. PACAP(-/-) mice were segregated into two groups based on mortality as well as body weight gain: PACAP(-/-) that survived >20 days of age with normal weight gain and PACAP(-/-) that died before 20 days with a marked weight loss. Kaplan-Meier survival analysis demonstrated that PACAP(-/-) mice and those carrying the PACAP transgene have similarly lower survival probability compared with their heterozygous littermates that served as positive controls. Further study using additional tissue-specific transgenic or knockout mouse models will be required to determine the causative defects underlying the high mortality of PACAP(-/-) mice.
Shintani
Norihito
N
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Hashimoto
Hitoshi
H
Tanaka
Kazuhiro
K
Kawaguchi
Chihiro
C
Tomimoto
Shuhei
S
Baba
Akemichi
A
D000818:Animals; D001483:Base Sequence; D003433:Crosses, Genetic; D004247:DNA / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D009479:Neuropeptides / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D010179:Pancreas / Q000502:physiology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D015430:Weight Gain
C495402:Adcyap1 protein, mouse; D009414:Nerve Growth Factors; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D004247:DNA