NOD.Cg-Tg(Ins2*Y16A)1Ell Ins1^tm1Jja Ins2^tm1Jja/GseJ

Stock number: 005524
Product name: NOD.Tg B:16 alanine, line B (low), Ins1^null, Ins2^null
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

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).

Detailed description

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.

Development

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.

Allele

Symbol: Tg(Ins2*Y16A)1Ell
Name: transgene insertion 1, John F Elliot
MGI accession ID: MGI:3576358
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(Ins2*Y16A)1Ell
Marker name: transgene insertion 1, John F Elliot
Chromosome: UN
Strain of origin: NOD/MrkTac
Expressed genes: Ins2,insulin 2,rat
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.

Allele

Symbol: Ins2^tm1Jja
Name: targeted mutation 1, Jacques Jami
MGI accession ID: MGI:2181878
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Ins2
Marker name: insulin II
Chromosome: 7
Strain of origin: 129S2/SvPas
Expressed genes: lacZ,beta-galactosidase,E. coli
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.

Allele

Symbol: Ins1^tm1Jja
Name: targeted mutation 1, Jacques Jami
MGI accession ID: MGI:2181877
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ins1
Marker name: insulin I
Chromosome: 19
Strain of origin: 129S2/SvPas
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.