The IsletTester mouse: an immunodeficient model with stable hyperglycemia for the study of human islets

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Item Type:	Article
Title:	The IsletTester mouse: an immunodeficient model with stable hyperglycemia for the study of human islets
Creators Name:	Waite, E.L., Tigue, M., Yu, M., Lahori, D., Kelly, K., May, C.L., Naji, A., Roman, J., Doliba, N., Avrahami, D., Nguyen-Ngoc, K.V., Sander, M., Glaser, B. and Kaestner, K.H.
Abstract:	The gold standard for assessing the function of human islets or β-like cells derived from stem cells involves their engraftment under the kidney capsule of hyperglycemic, immunodeficient mice. Current models, such as Streptozotocin (STZ) treatment of severely immunodeficient mice or the NRG-Akita strain are limited due to unstable and variable hyperglycemia and/or high morbidity of these models. To address these limitations, we developed the IsletTester mouse via CRISPRCas9 mediated gene editing of glucokinase (Gck), the glucose sensor of the β-cells, directly in NSG zygotes. IsletTester mice are heterozygous for an Arg345->stop mutation in Gck and present with stable random hyperglycemia (~250mg/dl; ~14 mM), normal life span and fertility. We demonstrate the utility of this model through functional engraftment of both human islets and hESC-derived β-like cells. The IsletTester mouse will enable the study of human islet biology over time and under different physiological conditions and can provide a useful preclinical platform to determine the functionality of stem cell-derived islet products.
Keywords:	Animals, Mice
Source:	Diabetes
ISSN:	0012-1797
Publisher:	American Diabetes Association
Page Range:	db230887
Date:	21 November 2024
Official Publication:	https://doi.org/10.2337/db23-0887
PubMed:	View item in PubMed

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