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Insulin2Q104del (Kuma) mutant mice develop diabetes with dominant inheritance.

Abstract：

:Insulin gene mutations have been identified to cause monogenic diabetes, and most of which developed permanent neonatal diabetes at young ages before 6 months of age in humans. To establish an animal model of permanent diabetes, we performed genome editing using the CRISPR/Cas9 system. We generated a novel Kuma mutant mice with p.Q104del in the Insulin2 (Ins2) gene in a BRJ background that exhibits a severe immune deficiency. Kuma mutant mice are non-obese and developed hyperglycemia from 3 weeks after birth in both males and females, which are inherited in a dominant mode. Kuma mutant mice displayed reduced insulin protein levels from 3-weeks-old, which seem to be caused by the low stability of the mutant insulin protein. Kuma mutant showed a reduction in islet size and islet mass. Electron microscopic analysis revealed a marked decrease in the number and size of insulin granules in the beta-cells of the mutant mice. Hyperglycemia of the mutant can be rescued by insulin administration. Our results present a novel insulin mutation that causes permanent early-onset diabetes, which provides a model useful for islet transplantation studies.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Sakano D,Inoue A,Enomoto T,Imasaka M,Okada S,Yokota M,Koike M,Araki K,Kume S

doi

10.1038/s41598-020-68987-z

subject

Has Abstract

pub_date

2020-07-22 00:00:00

pages

12187

issue

1

issn

2045-2322

pii

10.1038/s41598-020-68987-z

journal_volume

10

pub_type

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