These double knock-out Line B mice carry two knock-out insulin genes, Ins1 and Ins2 along with a transgene expressing a mutated insulin. Female transgenic mice fail to produce insulin autoantibodies, and show no diabetes or insulitis. Sialitis is expressed at a lower level than Line F (Stock No. 005525).
George Eisenbarth, U of Colorado
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Ins1 | insulin I |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Reporter, Null/Knockout) | Ins2 | insulin II |
Allele Type |
---|
Transgenic (Inserted expressed sequence) |
Transgenic mice reportedly express the mutant Ins2*Y16A protein in the pancreatic islets and thymus. The donating investigator reports approximately 75% of female transgenic mice (founder line B) become diabetic in the presence of native insulin genes by 35 weeks of age. In contrast, NOD female transgenic mice lacking both Ins1 and Ins2 fail to produce insulin autoantibodies, and neither diabetes nor insulitis develops by 26 weeks of age. Sialitis does occur, however. Line B transgenics have lower expression levels than line F (see Stock No. 005525), and 50% of the line B male transgenics lacking both Ins1 and Ins2 develop metabolic diabetes, with little to no insulitis, before 10 weeks of age.
This strain is useful to study insulin-reactive autoimmunity.
In the transgenic construct the rat insulin 7 promoter is fused to a mutated preproinsulin II cDNA encoding a tyrosine to alanine amino acid substitution at position 16 of the b chain. This transgene was microinjected directly into NOD/MrkTac oocytes (Nakayama et al, 2004). Offspring from the founder line B was further crossed to NOD.Ins1-/- and NOD.Ins2-/- to generate this double mutant, transgenic strain In 2006, the T1DR received the double mutant transgenic strain at generation N10F7.
Expressed Gene | lacZ, beta-galactosidase, E. coli |
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Site of Expression | |
Expressed Gene | Ins2, insulin 2, rat |
Site of Expression |
Allele Name | targeted mutation 1, Jacques Jami |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Ins1- |
Gene Symbol and Name | Ins1, insulin I |
Gene Synonym(s) | |
Strain of Origin | 129S2/SvPas |
Chromosome | 19 |
Molecular Note | The majority of the coding region was replaced with a neomycin selection cassette. RT-PCR analysis showed an absence of transcript in homozygous mutant mice. |
Mutations Made By | Jacques Jami, INSERM |
Allele Name | targeted mutation 1, Jacques Jami |
---|---|
Allele Type | Targeted (Reporter, Null/Knockout) |
Allele Synonym(s) | Ins2-; proins-2-; proinsulin 2- |
Gene Symbol and Name | Ins2, insulin II |
Gene Synonym(s) | |
Expressed Gene | lacZ, beta-galactosidase, E. coli |
Strain of Origin | 129S2/SvPas |
Chromosome | 7 |
Molecular Note | The majority of the coding region was replaced by the insertion of a lacZ-neo fusion gene. The expression of lacZ was found to be under the control of the endogenous promoter via cytochemical assays. |
Mutations Made By | Jacques Jami, INSERM |
Allele Name | transgene insertion 1, John F Elliot |
---|---|
Allele Type | Transgenic (Inserted expressed sequence) |
Allele Synonym(s) | tg B:16 alanine, line B |
Gene Symbol and Name | Tg(Ins2*Y16A)1Ell, transgene insertion 1, John F Elliot |
Gene Synonym(s) | |
Promoter | Ins2, insulin 2, rat |
Expressed Gene | Ins2, insulin 2, rat |
Strain of Origin | NOD/MrkTac |
Chromosome | UN |
Molecular Note | This transgenic construct contains the rat insulin7 construct of the rat insulin 2 gene fused to a mutated preproinsulin II cDNA where the tyrosine at position 16 of the B chain was replaced with alanine. The transgene is expressed in pancreatic beta cells. |
Mutations Made By | John Elliott, University of Alberta |
When using the NOD.Tg B:16 alanine, line B (low), Ins1null, Ins2null mouse strain in a publication, please cite the originating article(s) and include JAX stock #005524 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Hemizygous for Tg(Ins2*Y16A)1Ell, Heterozygous for Ins1<tm1Jja>, Heterozygous or Wild-type for Ins2<tm1Jja> |
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