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dc.contributor.authorPearson, Todd
dc.contributor.authorShultz, Leonard D.
dc.contributor.authorLief, J.
dc.contributor.authorBurzenski, Lisa M.
dc.contributor.authorGott, Bruce
dc.contributor.authorChase, T.
dc.contributor.authorForeman, Oded
dc.contributor.authorRossini, Aldo A.
dc.contributor.authorBottino, Rita
dc.contributor.authorTrucco, Massimo
dc.contributor.authorGreiner, Dale L.
dc.date2022-08-11T08:09:38.000
dc.date.accessioned2022-08-23T16:38:14Z
dc.date.available2022-08-23T16:38:14Z
dc.date.issued2008-06-20
dc.date.submitted2009-11-09
dc.identifier.citation<p>Diabetologia. 2008 Aug;51(8):1449-56. Epub 2008 Jun 19. <a href="http://dx.doi.org/10.1007/s00125-008-1057-1">Link to article on publisher's site</a></p>
dc.identifier.issn0012-186X (Print)
dc.identifier.doi10.1007/s00125-008-1057-1
dc.identifier.pmid18563383
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39202
dc.description.abstractAIMS/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-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. RESULTS: NOD-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/INTERPRETATION: The 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=18563383&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2719841/
dc.subjectAnimals
dc.subjectCord Blood Stem Cell Transplantation
dc.subjectDisease Models, Animal
dc.subjectHumans
dc.subjectHyperglycemia
dc.subjectInsulin-Secreting Cells
dc.subjectIslets of Langerhans
dc.subject*Islets of Langerhans Transplantation
dc.subjectMice
dc.subjectMice, Inbred NOD
dc.subject*Mutation
dc.subjectReceptors, Interleukin-2
dc.subjectSevere Combined Immunodeficiency
dc.subjectTransplantation, Heterologous
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleA new immunodeficient hyperglycaemic mouse model based on the Ins2Akita mutation for analyses of human islet and beta stem and progenitor cell function
dc.typeJournal Article
dc.source.journaltitleDiabetologia
dc.source.volume51
dc.source.issue8
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2009
dc.identifier.contextkey1058083
html.description.abstract<p>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.</p> <p>METHODS: We 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.</p> <p>RESULTS: NOD-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.</p> <p>CONCLUSIONS/INTERPRETATION: The 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.</p>
dc.identifier.submissionpathoapubs/2009
dc.contributor.departmentDepartment of Medicine, Division of Diabetes
dc.source.pages1449-56


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