Published in:
01-11-2010 | Short Communication
A mutation in KCNJ11 causing human hyperinsulinism (Y12X) results in a glucose-intolerant phenotype in the mouse
Published in: Diabetologia | Issue 11/2010
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Aims/hypothesis
We identified a mouse with a point mutation (Y12STOP) in the Kcnj11 subunit of the KATP channel. This point mutation is identical to that found in a patient with congenital hyperinsulinism of infancy (HI). We aimed to characterise the phenotype arising from this loss-of-function mutation and to compare it with that of other mouse models and patients with HI.
Methods
We phenotyped an N-ethyl-N-nitrosourea-induced mutation on a C3H/HeH background (Kcnj11
Y12STOP
) using intraperitoneal glucose tolerance testing to measure glucose and insulin plasma concentrations. Insulin secretion and response to incretins were measured on isolated islets.
Results
Homozygous male and female adult Kcnj11
Y12STOP
mice exhibited impaired glucose tolerance and a defect in insulin secretion as measured in vivo and in vitro. Islets had an impaired incretin response and reduced insulin content.
Conclusions/interpretation
The phenotype of homozygous Kcnj11
Y12STOP
mice is consistent with that of other Kcnj11-knockout mouse models. In contrast to the patient carrying this mutation homozygously, the mice studied did not have hyperinsulinaemia or hypoglycaemia. It has been reported that HI patients may develop diabetes and our mouse model may reflect this clinical feature. The Kcnj11
Y12STOP
model may thus be useful in further studies of KATP channel function in various cell types and in investigation of the development of hyperglycaemia in HI patients.