Evidence map›Paper›PMID 39571094›Full record

ArticleDiabetes2025

The IsletTester Mouse: An Immunodeficient Model With Stable Hyperglycemia for the Study of Human Islets.

Eric L Waite, Mark Tigue, Ming Yu, Deeksha Lahori, Kai Kelly, Catherine Lee May, Ali Naji, Jeffrey Roman, Nicolai Doliba, Dana Avrahami and 4 more

Abstract read
In one paragraph

Article in Diabetes, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Eric L WaiteInstitute of Diabetes, Obesity, and Metabolism, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA.ORCID 0000-0003-3023-3641
Mark TigueInstitute of Diabetes, Obesity, and Metabolism, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA.
Ming YuInstitute of Diabetes, Obesity, and Metabolism, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA.
Deeksha LahoriInstitute of Diabetes, Obesity, and Metabolism, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA.
Kai KellyInstitute of Diabetes, Obesity, and Metabolism, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA.
Catherine Lee MayInstitute of Diabetes, Obesity, and Metabolism, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA.
Ali NajiInstitute of Diabetes, Obesity, and Metabolism, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA.
Jeffrey RomanInstitute of Diabetes, Obesity, and Metabolism, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA.
Nicolai DolibaInstitute of Diabetes, Obesity, and Metabolism, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA.
Dana AvrahamiDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Kim-Vy Nguyen-NgocDepartments of Pediatrics and Cellular and Molecular Medicine, Pediatric Diabetes Research Center, University of California, San Diego, La Jolla, CA.
Maike SanderDepartments of Pediatrics and Cellular and Molecular Medicine, Pediatric Diabetes Research Center, University of California, San Diego, La Jolla, CA.
Benjamin GlaserDepartment of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel.ORCID 0000-0003-4711-5000
Klaus H KaestnerInstitute of Diabetes, Obesity, and Metabolism, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA.ORCID 0000-0002-1228-021X

Funding

VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI DOUGLAS J EPSTEIN · 1986 to 2026
$48.3M
TRANSGENIC AND CHIMERIC MOUSE COREP30DK050306 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GARY D. WU · 1997 to 2026
$32.5M
The Human Pancreas Analysis Program for Type 2 DiabetesU01DK123594 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Robert Babak Faryabi, KLAUS H KAESTNER · 2019 to 2026
$25.0M
Functional Interrogation of T2D-associated genes in human stem cell-derived models and miceUM1DK126194 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GRANT, STRUAN F A, KAESTNER, KLAUS H · 2020 to 2024
$8.8M
The role of senescent beta cells in T1D and T2DU01DK134995 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KAESTNER, KLAUS H · 2022 to 2025
$2.8M
A 3D vascularized islet biomimetic to model type 1 diabetesUG3DK122639 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HUGHES, CHRISTOPHER C. W., SANDER, MAIKE · 2019 to 2020
$2.1M
Drivers and consequences of beta cell DNA damage in type 1 diabetesUC4DK116271 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KAESTNER, KLAUS H · 2017 to 2017
$1.7M
Israel Science Foundation 1782/18NIDDK NIH HHS 5UG3DK122639NIDDK NIH HHS P30 DK019525NIDDK NIH HHS P30 DK050306NIDDK NIH HHS U01 DK123594NIDDK NIH HHS U01 DK134995NIDDK NIH HHS UC4 DK116271NIDDK NIH HHS UG3 DK122639NIDDK NIH HHS UM1 DK126194United States-Israel Binational Science Foundation 2019314
6 · The paper itself

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 treatment of severely immunodeficient mice or the NRG-Akita strain, are limited due to unstable and variable hyperglycemia and/or high morbidity. To address these limitations, we developed the IsletTester mouse via CRISPR/Cas9-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 (∼250 mg/dL [14 mmol/L]), normal lifespan, and fertility. We demonstrate the utility of this model through functional engraftment of both human islets and human embryonic stem cell-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. ARTICLE HIGHLIGHTS: Current mouse models for assessing islet function in vivo are limited due to unstable and variable hyperglycemia and/or high morbidity. We derived the IsletTester mouse to address these limitations. Leveraging a previously characterized glucokinase mutation and CRISPR/Cas9 technology, we successfully developed a moderately hyperglycemic and immunodeficient mouse model for the in vivo assessment of islet function. Our IsletTester mouse has stable, moderate hyperglycemia that can be corrected with primary human islets or stem cell-derived insulin-producing cells. The IsletTester mouse provides a reliable, easy-to-use platform for the preclinical assessment of stem cell-derived islet products or islet-targeted drugs.

Indexed as

HyperglycemiaInsulin-Secreting CellsIslets of LangerhansIslets of Langerhans TransplantationAnimalsCRISPR-Cas SystemsDisease Models, AnimalFemaleGene EditingGlucokinaseHumansMiceMice, Inbred NODGlucokinase

Identifiers

PMID39571094
PMCPMC11842601

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.