| First Author | Pearson T | Year | 2008 |
| Journal | Diabetologia | Volume | 51 |
| Issue | 8 | Pages | 1449-56 |
| PubMed ID | 18563383 | Mgi Jnum | J:138005 |
| Mgi Id | MGI:3803541 | Doi | 10.1007/s00125-008-1057-1 |
| Citation | Pearson T, et al. (2008) A new immunodeficient hyperglycaemic mouse model based on the Ins2 ( Akita ) mutation for analyses of human islet and beta stem and progenitor cell function. Diabetologia 51(8):1449-56 |
| abstractText | AIMS/HYPOTHESIS: To 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. METHODS: We generated and characterised a new strain of immunodeficient spontaneously hyperglycaemic mice, the NOD-Rag1 ( null ) Prf1 ( null ) Ins2 ( Akita ) strain and compared this strain with the NOD-scid Il2rgamma ( null ) (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. RESULTS: NOD-Rag1 ( null ) Prf1 ( null ) Ins2 ( Akita ) mice developed spontaneous hyperglycaemia, similar to Ins2 ( Akita )-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-Rag1 ( null ) Prf1 ( null ) Ins2 ( Akita ) and chemically diabetic NOD-scid Il2rgamma ( null ) mice resulted in a return to euglycaemia that occurred with transplantation of similar beta cell masses. CONCLUSIONS/INTERPRETATION: The NOD-Rag1 ( null ) Prf1 ( null ) Ins2 ( Akita ) mouse is the first immunodeficient, spontaneously hyperglycaemic mouse strain described that is based on the Ins2 ( Akita ) 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. |
