ArticleDiabetologia2008
A new immunodeficient hyperglycaemic mouse model based on the Ins2Akita mutation for analyses of human islet and beta stem and progenitor cell function.
Article in Diabetologia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- A Novel Immunodeficient Hyperglycemic Mouse Carrying the Ins1 Akita Mutation for Xenogeneic Islet Cell Transplantation.Transplantation · 2025Article
- Enhancing islet transplantation using a biocompatible collagen-PDMS bioscaffold enriched with dexamethasone-microplates.Biofabrication · 2021Article
- Recovery of viable endocrine-specific cells and transcriptomes from human pancreatic islet-engrafted mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Stem cell-derived extracellular vesicles inhibit and revert fibrosis progression in a mouse model of diabetic nephropathy.Scientific reports · 2019Article
- Crimean-Congo haemorrhagic fever virus: Past, present and future insights for animal modelling and medical countermeasures.Zoonoses and public health · 2018Review
- Human islet xenotransplantation in rodents: A literature review of experimental model trends.Clinics (Sao Paulo, Brazil) · 2017Review
- Stress and the inflammatory process: a major cause of pancreatic cell death in type 2 diabetes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2014Review
- Genetic and Pharmacologic Models for Type 1 Diabetes.Current protocols in mouse biology · 2013Article
- Porous scaffolds support extrahepatic human islet transplantation, engraftment, and function in mice.Cell transplantation · 2013Article
- Advancing animal models of human type 1 diabetes by engraftment of functional human tissues in immunodeficient mice.Cold Spring Harbor perspectives in medicine · 2012Review
- Human islet cell MORF/cMORF pretargeting in a xenogeneic murine transplant model.Molecular pharmaceutics · 2011Article
- Article
- Humanized mouse models to study human diseases.Current opinion in endocrinology, diabetes, and obesity · 2010Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
aims/hypothesisTo develop and validate a new immunodeficient mouse strain that spontaneously develops a non-autoimmune hyperglycaemia to serve as a diabetic host for human islets and human beta stem and progenitor cells without the need for induction of hyperglycaemia by toxic chemicals with their associated side effects.
methodsWe generated and characterised a new strain of immunodeficient spontaneously hyperglycaemic mice, the NOD-Rag1null Prf1null Ins2Akita strain and compared this strain with the NOD-scid Il2rgammanull (also known as Il2rg) immunodeficient strain rendered hyperglycaemic by administration of a single dose of streptozotocin. Hyperglycaemic mice were transplanted with human islets ranging from 1,000 to 4,000 islet equivalents (IEQ) and were monitored for normalisation of blood glucose levels.
resultsNOD-Rag1null Prf1null Ins2Akita mice developed spontaneous hyperglycaemia, similar to Ins2Akita-harbouring strains of immunocompetent mice. Histological examination of islets in the host pancreas validated the spontaneous loss of beta cell mass in the absence of mononuclear cell infiltration. Human islets transplanted into spontaneously diabetic NOD-Rag1null Prf1null Ins2Akita and chemically diabetic NOD-scid Il2rgammanull mice resulted in a return to euglycaemia that occurred with transplantation of similar beta cell masses. CONCLUSIONS/
interpretationThe NOD-Rag1null Prf1null Ins2Akita mouse is the first immunodeficient, spontaneously hyperglycaemic mouse strain described that is based on the Ins2Akita mutation. This strain is suitable as hosts for human islet and human beta stem and progenitor cell transplantation in the absence of the need for pharmacological induction of diabetes. This strain of mice also has low levels of innate immunity and can be engrafted with a human immune system for the study of human islet allograft rejection.
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