Open AccessPhenotypic alterations in insulin-deficient mutant mice
Author(s) -
Bertrand Duvillié,
Nathalie Cordonnier,
Louise Deltour,
Françoise Dandoy-Dron,
Jean-Michel Itier,
Eliane Monthioux,
Jacques Jami,
Rajiv L. Joshi,
Danielle Bucchini
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.10.5137
Subject(s) - medicine , endocrinology , biology , insulin , pancreatic polypeptide , glucagon , glucokinase , somatostatin , pancreas , enteroendocrine cell , islet , pancreatic islets , pancreatic hormone , endocrine system , hormone , insulin resistance
Two mouse insulin genes,Ins1 andIns2 , were disrupted andlacZ was inserted at theIns2 locus by gene targeting. Double nullizygous insulin-deficient pups were growth-retarded. They did not show any glycosuria at birth but soon after suckling developed diabetes mellitus with ketoacidosis and liver steatosis and died within 48 h. Interestingly, insulin deficiency did not preclude pancreas organogenesis and the appearance of the various cell types of the endocrine pancreas. The presence oflacZ expressing β cells and glucagon-positive α cells was demonstrated by cytochemistry and immunocytochemistry. Reverse transcription-coupled PCR analysis showed that somatostatin and pancreatic polypeptide mRNAs were present, although at reduced levels, accounting for the presence also of δ and pancreatic polypeptide cells, respectively. Morphometric analysis revealed enlarged islets of Langherans in the pancreas from insulin-deficient pups, suggesting that insulin might function as a negative regulator of islet cell growth. Whether insulin controls the growth of specific islet cell types and the molecular basis for this action remain to be elucidated.