Compensatory responses in mice carrying a null mutation for Ins1 or Ins2.
Intrauterine growth retardation and postnatal acute diabetes result from insulin deficiency in double homozygous null mutants for Ins1 and Ins2 (Duvillié B, et al., Proc. Natl. Acad. Sci. USA 94:5137-5140, 1997). The characterization of single homozygous null mutants for Ins1 or Ins2 is described here. Neither kind of mutant mice was diabetic. Immunocytochemical analysis of the islets showed normal distribution of the endocrine cells producing insulin, glucagon, somatostatin, or pancreatic polypeptide. Analysis of the expression of the functional insulin gene in Ins1-/- or Ins2-/- mice revealed a dramatic increase of Ins1 transcripts in Ins2-/- mutants. This compensatory response was quantitatively reflected by total pancreatic insulin content similar for both types of mutants and wild-type mice. Moreover, both mutants had normal plasma insulin levels and normal glucose tolerance tests. The determination of beta-cell mass by morphometry indicated beta-cell hyperplasia in the mutant mice. The beta-cell mass in Ins2-/- mice was increased almost threefold, which accounts for the increase of Ins1 transcripts in Ins2-/-mutants. This study thus contributes to evaluate the potential of increasing the beta-cell mass to compensate for low insulin production.
Department of Genetics, Development and Molecular Pathology, ICGM, Institut National de la Santé et de la Recherche Médicale Unit 257, Paris, France.
L
L
Leroux
P
P
Desbois
L
L
Lamotte
B
B
Duvillié
N
N
Cordonnier
M
M
Jackerott
J
J
Jami
D
D
Bucchini
R L
RL
Joshi
D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D005260:Female; D015870:Gene Expression; D005934:Glucagon / Q000032:analysis; D006965:Hyperplasia / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood / Q000172:deficiency / Q000235:genetics*; D007515:Islets of Langerhans / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009154:Mutation; D010191:Pancreatic Polypeptide / Q000032:analysis; D011384:Proinsulin / Q000032:analysis; D012313:RNA / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000032:analysis
D007328:Insulin; D013004:Somatostatin; D010191:Pancreatic Polypeptide; D012313:RNA; D005934:Glucagon; D011384:Proinsulin