NOD.Cg-Tg(Ins2*Y16A)3Ell Ins1^tm1Jja Ins2^tm1Jja/GseJ

Stock number: 005525
Product name: NOD.Tg B:16 alanine, line F (high), Ins1^null, Ins2^null
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These double knock-out Line F 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 higher level than Line B (Stock No. 005524).

Detailed description

Expression has been reported in the pancreatic islets and thymus of NOD mice carrying the Tg(Ins2*Y16A)3Ell mutation. Approximately 15% of line F female transgenic mice become diabetic in the presence of native insulin genes by 35 weeks of age. NOD female transgenic mice lacking both Ins1 and Ins2 fail to produce insulin autoantibodies, and there is no diabetes or insulitis at 26 weeks of age, but sialitis is present. In contrast, transgenic mice in the presence of Ins1 and lacking Ins2 develop diabetes in 75% of the animals by 25 weeks of age (Nakayama et al, 2004, 2005).

This stock is useful to study insulin-reactive autoimmunity.

Development

NOD-Tg(Ins2*Y16A)3Ell/GseJ expresses the rat insulin 7 promoter fused to a mutated preproinsulin II cDNA, where the tyrosine at position 16 of the b chain was replaced with alanine. This transgene was inserted by Nakayama et al, 2004 directly into NOD/MrkTac oocytes. Offspring from the founder line F was further crossed to NOD.Ins1-/- and NOD.Ins2-/- prior to intercrossing for homozygosity of the Ins1 and Ins2 targeted mutations. In 2006, the T1DR received NOD.Cg-Tg(Ins2*Y16A)3Ell Ins1^tm1Jja Ins2^tm1Jja/GseJ at generation N10F9.

Allele

Symbol: Tg(Ins2*Y16A)3Ell
Name: transgene insertion 3, John F Elliot
MGI accession ID: MGI:3576273
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(Ins2*Y16A)3Ell
Marker name: transgene insertion 3, 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.