title: Characterization of intestinal and pancreatic dysfunction in VPAC1-null mutant mouse.
abstract: OBJECTIVE
  These studies examined the effect of homozygous deletion of vasoactive intestinal peptide receptor type 1 (VPAC1) on development and function of intestines and pancreas.
  
  
  METHODS
  Genetically engineered VPAC1-null mutant mice were monitored for growth, development, and glucose homeostasis. Expression of VPAC1 was examined during embryonic development using VPAC1 promoter-driven β-galactosidase transgenic mice.
  
  
  RESULTS
  Homozygous deletion of VPAC1 resulted in fetal, neonatal, and postweaning death owing to failure to thrive, intestinal obstruction, and hypoglycemia. Histological findings demonstrated disorganized hyperproliferation of intestinal epithelial cells with mucus deposition and bowel wall thickening. The pancreas demonstrated small dysmorphic islets of Langerhans containing α, β, and δ cells. Expression of a VPAC1 promoter-driven transgene was observed in E12.5 and E14.5 intestinal epithelial and pancreatic endocrine cells. Vasoactive intestinal peptide receptor type 1-null mutant animals had lower baseline blood glucose levels compared to both heterozygous and wild-type littermates. Vasoactive intestinal peptide receptor type 1-deficient mice responded to oral glucose challenge with normal rise in blood glucose followed by rapid hypoglycemia and failure to restore baseline glucose levels. Insulin challenge resulted in profound hypoglycemia and inadequate glucose homeostasis in VPAC1-null mutant animals.
  
  
  CONCLUSIONS
  These observations support a role for VPAC1 during embryonic and neonatal development of intestines and endocrine pancreas.
authors.affiliation: Department of Immunology, University of Ulm, Ulm, Germany.
authors.forename: Dorit
authors.initials: D
authors.lastname: Fabricius
authors.forename: Bahri
authors.initials: B
authors.lastname: Karacay
authors.forename: Damon
authors.initials: D
authors.lastname: Shutt
authors.forename: Whitney
authors.initials: W
authors.lastname: Leverich
authors.forename: Blanca
authors.initials: B
authors.lastname: Schafer
authors.forename: Erika
authors.initials: E
authors.lastname: Takle
authors.forename: Daniel
authors.initials: D
authors.lastname: Thedens
authors.forename: Geetika
authors.initials: G
authors.lastname: Khanna
authors.forename: Sudhanshu
authors.initials: S
authors.lastname: Raikwar
authors.forename: Baoli
authors.initials: B
authors.lastname: Yang
authors.forename: Mary E
authors.initials: ME
authors.lastname: Desmond
authors.forename: Mary Sue
authors.initials: MS
authors.lastname: O'Dorisio
mesh_terms: D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D005951:Glucose Tolerance Test; D006579:Heterozygote; D006720:Homozygote; D007422:Intestines / Q000196:embryology* / Q000473:pathology / Q000503:physiopathology*; D007515:Islets of Langerhans / Q000196:embryology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010179:Pancreas / Q000196:embryology* / Q000473:pathology / Q000503:physiopathology*; D011247:Pregnancy; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
chemical_list: D001786:Blood Glucose; D017931:DNA Primers; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I