Phenotypic alterations in insulin-deficient mutant mice

Two mouse insulin genes, Ins1 and Ins2, were disrupted and lacZ was inserted at the Ins2 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...

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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 94; no. 10; pp. 5137 - 5140
Main Authors:	Duvillie, B. (Institut National de la Sante et de la Recherche Medicale, Paris, France.), Cordonnier, N, Deltour, L, Dandoy-Dron, F, Itier, J.M, Monthioux, E, Jami, J, Joshi, R.L, Bucchini, D
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences of the United States of America 13-05-1997 National Acad Sciences National Academy of Sciences The National Academy of Sciences of the USA
Subjects:	Animals Animals, Newborn ARN MENSAJERO ARN MESSAGER BETA GALACTOSIDASA BETA GALACTOSIDASE beta-Galactosidase - biosynthesis beta-Galactosidase - genetics Biological Sciences Biology Bone Development Cell growth CHIMIE Death DIABETE DIABETES Diabetes Mellitus, Type 1 - genetics Diabetes Mellitus, Type 1 - pathology Diabetes Mellitus, Type 1 - physiopathology DNA Primers Embryos FENOTIPOS Gamma cells GENE GENES Growth Disorders - genetics Growth Disorders - pathology Growth Disorders - physiopathology Heterozygote HIGADO GRASO HORMONAS HORMONE IMMUNOLOGIE INMUNOLOGIA Insulin Insulin - deficiency Insulin - genetics INSULINA INSULINE Islet cells Islets of Langerhans - metabolism Islets of Langerhans - pathology Life Sciences Liver - pathology Messenger RNA Mice Mice, Knockout Mice, Transgenic MUTACION MUTANT MUTANTES MUTATION PANCREAS PHENOTYPE Polymerase Chain Reaction Pups QUIMICA RATON Receptors Rodents SOMATOSTATINA SOMATOSTATINE SOURIS STEATOSE HEPATIQUE TRASTORNOS METABOLICOS TROUBLE DU METABOLISME
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Summary:	Two mouse insulin genes, Ins1 and Ins2, were disrupted and lacZ was inserted at the Ins2 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 of lacZ expressing beta cells and glucagon-positive alpha 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 delta 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
Bibliography:	S30 9744533 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 PMCID: PMC24644 To whom reprint requests should be addressed. Donald F. Steiner, University of Chicago, Chicago, IL B.D. and N.C. contributed equally to this work.
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.94.10.5137