These Akita Rag1 double mutant mice exhibit the diabetes phenotype in the absence of B and T cells. and do not reject allografts.
Dr. Leonard D. Shultz, The Jackson Laboratory
Mice homozygous for the Rag1 targeted mutation and heterozygous for the Akita spontaneous display the diabetes phenotype in the absence of B and T cells and unlike single Akita mice, double mutants do not reject allografts. Mice heterozygous for only the Akita spontaneous mutation are viable and fertile. (Homozygotes typically die by 12 weeks of age from extreme hyperglycemia.) Symptoms in heterozygous mutant mice include hyperglycemia, hypoinsulinemia, polydipsia, and polyuria, beginning at approximately 3-4 weeks of age. The diabetic phenotype is more severe and progressive in heterozygous males than in females. Obesity and insulitis do not accompany diabetes.
This double mutant strain is ideally suited for use in allogeneic or xenogeneic islet or stem cell transplantation protocols because the mice are severely immunocompromised and spontaneously develop diabetes at a young age.
|Allele Synonym(s)||Akita; AkitaIns2; Ins2C96Y; Ins2Mody; Mody; Mody4|
|Gene Symbol and Name||Ins2, insulin II|
|Gene Synonym(s)||AA986540; CP-II; IDDM; IDDM1; IDDM2; ILPR; IRDN; Ins-2; Ins-2; InsII; MODY10; Mody; Mody; Mody4; Mody4; expressed sequence AA986540; maturity onset diabetes of the young; maturity onset diabetes of the young 4|
|Strain of Origin||C57BL/6NSlc|
|Molecular Note||In the mutant allele a transition from G to A at nucleotide 1907 disrupted an Fnu4HI site in exon 3. This mutation changed the seventh amino acid in the A chain of mature insulin, Cys96 (TGC), to Tyr (TAC). The authors predict that the transition would disrupt a disulfide bond between the A and the B chains and would likely induce a major conformational change in insulin 2 molecules. RT-PCR studies suggest that both normal and mutant Ins2 alleles are transcribed similarly in pancreatic islets of heterozygous mice, although immunofluorescence and immunoblot analyses of heterozygous islets detected reduced levels of insulin and proinsulin.|
|Allele Name||targeted mutation 1, Peter Mombaerts|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||RAG-1-; RAG1null; Rag-; Rag-1KO; Rag1-; Rag1tm1Mom|
|Gene Symbol and Name||Rag1, recombination activating gene 1|
|Gene Synonym(s)||RAG-1; RNF74; Rag-1; Rag-1|
|Site of Expression||expression is seen in bone marrow derived cell lines.|
|Strain of Origin||129S7/SvEvBrd-Hprt<+>|
|Molecular Note||A 1356 bp genomic fragment of the Rag1 gene, encoding the nuclear localization signal and the zinc-finger motif, was replaced by a neomycin cassette. A mutant transcript expressed from this allele was detected by Northern blot in bone marrow derived cell lines from homozygous mice.|
|Mutations Made By|| |
Peter Mombaerts, Max Planck Research Unit for Neurogenetics
This strain is maintained by breeding wildtype females (Rag1-/-Ins2+/+) to affected (hyperglycemic) males (Rag1-/-Ins2Akita/+). The Rag1tm1Mom allele is maintained in homozygosity and the Ins2Akita allele is maintained in heterozygosity. After onset of diabetes, when cages become very wet due to polyuria, the health of Ins2Akita heterozygotes is best maintained by housing them individually in cages containing a mixture of regular litter and Alpha-Dri, changed twice weekly. Specific pathogen free (SPF) conditions are recommended. Expected coat color is Black.
When using the B6.Cg-Rag1tm1Mom Ins2Akita/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #004369 in your Materials and Methods section.
|Heterozygous or Wild-type for Rag1<tm1Mom>, Heterozygous or Wild-type for Ins2<Akita>|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of
each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders
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