These NOD.scid RIP-GAD A-line mice express a transgene containing the human glutamic acid decarboxylase (GAD65) and exhibit a markedly lowered incidence of diabetes.
Dr. Edward Leiter, The Jackson Laboratory
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Spontaneous | Prkdc | protein kinase, DNA activated, catalytic polypeptide |
Allele Type |
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Transgenic (Inserted expressed sequence, Humanized sequence) |
NOD.Cg-Prkdcscid Tg(Ins2-GAD2)2Lt/LtJ transgenic mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. Transgenic mice are homozygous for Prkdcscid and are free of potential insulitic lymphocytes resulting in diabetes resistance. Delayed diabetes onset is observed when splenic lymphocytes from 5 week old pre-diabetic NOD females are adoptively transferred into NOD transgenic mice homozygote for Prkdcscid when compared to adoptive transfers into control NOD females. Similar to the NOD/ShiLt(Cg)-Tg(Ins2-GAD2)2Lt/J (Stock No. 005870) homozygous transgenic mice are developmentally lethal due to the transgene insertion site (Bridgett et al, Diabetes 1998 47:1848-56).
This model provides a tool for studying the role of GAD2 as an islet autoantigen in the NOD mouse model of Type 1 diabetes.
The transgene Ins2-GAD2 encodes the human glutamic acid decarboxylase2 cDNA under the control of the rat insulin 2 promoter. This transgenic construct was injected into NOD/Lt oocytes and the resulting founders were backcrossed to wildtype siblings. NOD transgenic mice were backcrossed 1 generation to NOD.CB17-Prkdcscid prior to intercrossing to make homozygote for the Prkdcscid mutation (Bridgett et al, Diabetes 1998 47:1848-56). In 2005, the Type 1 Diabetes Resource received NOD/LtSz-Prkdcscid Tg(Ins2-GAD2)2Lt/LtJ at generation N2F31.
Expressed Gene | GAD2, glutamate decarboxylase 2, human |
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Site of Expression |
Allele Name | severe combined immunodeficiency |
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Allele Type | Spontaneous |
Allele Synonym(s) | SCID |
Gene Symbol and Name | Prkdc, protein kinase, DNA activated, catalytic polypeptide |
Gene Synonym(s) | |
Site of Expression | T and B lymphocytes. |
Strain of Origin | C.BKa-Ighb/Icr |
Chromosome | 16 |
Molecular Note | A T-to-A transversion point mutation at a position corresponding to codon 4046 (codon 4095 in transcript ENSMUST00000023352.8) created a premature stop codon (p.Y4046*). |
Allele Name | transgene insertion 2, Edward H Leiter |
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Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | TgN(RIP7hGAD65)Lt4 (A line); TgN(RIP7hGAD65)Lt4 A-line |
Gene Symbol and Name | Tg(Ins2-GAD2)2Lt, transgene insertion 2, Edward H Leiter |
Gene Synonym(s) | |
Promoter | Ins2, insulin 2, rat |
Expressed Gene | GAD2, glutamate decarboxylase 2, human |
Strain of Origin | NOD/ShiLt |
Chromosome | 15 |
Molecular Note | The transgene comprises the cDNA sequence encoding human glutamic acid decarboxylase 2 under control of a modified rat insulin 2 promoter composed of 9.5 kb of genomic DNA from upstream of the transcription initiation site fused to the first intron of Ins2. Densitrometric Southern blot analysis indicates presence of 4-5 copies of the transgene. FISH analysis and pseudo-Giemsa metaphase spread analysis showed integration to have occurred near the centromere of Chr 15. Expression in the pancreatic islets of transgenic mRNA has been demonstrated by reverse transcription followed by PCR (RT-PCR), and of GAD2 protein by western blot analysis. |
Mutations Made By | Dr. Edward Leiter, The Jackson Laboratory |
These mice are immunodeficient and need to be maintained in a high barrier environment with sterile food and water or given antibiotic in the water.
When using the NOD.scid RIP-GAD A-line mouse strain in a publication, please cite the originating article(s) and include JAX stock #003844 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Homozygous for Prkdc<scid>, Hemizygous or Non carrier for Tg(Ins2-GAD2)2Lt |
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