NODCaj.Cg-Ighm^tm1Cgn Tg(Igh-VB1-8/Igh-6m)1Mjsk/FswJ

Stock number: 005306
Product name: NOD.mIgM
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

A fraction of these transgenic mice show increased insulitis, and diabetes incidence is partially restored in females.

Detailed description

Transgenic mice carrying the Ighm^tm1Cgn allele are viable, fertile, and normal in size and restores the B220+ B-cells to normal. The number of B-cells is normal and the ratio of CD4 to CD8 is normal. Although only a fraction of the transgenic mice have an increased amount of insulitis, it is more severe, especially in males. Diabetes incidence is partially restored in NODCaj.Cg-Ighm^tm1Cgn Tg(Igh-VB1-8/Igh-6m)1Mjsk/Fsw with approximately, 11% females and 0% males becoming diabetic by 50 weeks of age compared to approximately 2% Ighm^tm1Cgn female controls and 0% Ighm^tm1Cgn male controls by 50 weeks of age or 90% female NOD controls and 70% male NOD controls by 30 weeks of age. T- cell depleted spleen cells from Ighm^tm1Cgn Tg(Igh-VB1-8/Igh-6m)1Mjsk mice stimulated with lipopolysaccharide (LPS) respond normally. NODCaj.Cg-Ighm^tm1Cgn Tg(Igh-VB1-8/Igh-6m )2Mjsk/Fsw like NOD.129S2(B6)-Ighm^tm1Cgn generate low T-cell responses to GAD and insulin.

This model is useful for separating the role of B-cells in antigen presentation from antibody production involved in diabetes development.

Development

The transgenic construct Tg(Igh-VB1-8/Igh-6m)1Mjsk that encodes a membrane bound, but not a secreted, immunoglobulin mu heavy chain, was injected into NOD/Caj zygotes. Founders were backcrossed to NOD/Caj. An outcross-intercross strategy was employed to introduce an inactivated Ighm allele from NOD.129S2(B6)-Ighm^tm1Cgn. In 2005, the Type 1 Diabetes Resource received NOD/Caj.Cg-Ighm^tm1Cgn Tg(Igh-VB1-8/Igh-6m)1Mjsk/FswJ at generation N12F3.

Allele

Symbol: Tg(Igh-VB1-8/Igh-6m)1Mjsk
Name: transgene insertion 1, Mark J Shlomchik
MGI accession ID: MGI:3578639
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(Igh-VB1-8/Igh-6m)1Mjsk
Marker name: transgene insertion 1, Mark J Shlomchik
Chromosome: UN
Strain of origin: NOD/Caj
Expressed genes: Ighm,immunoglobulin heavy constant mu,mouse, laboratory
Molecular note: The transgene encodes a membrane-bound, but not a secreted, immunoglobulin mu heavy chain. The variable region of the transgene comprises the VDJ moiety from the functionally rearranged Igh gene of the C57BL/6-derived B1-8 hybridoma, containing the V-region segment Vh186.2 and recognizing the hapten (4-hydroxy-3-nitrophenyl)acetyl. This is followed by a J-C intron fragment containing the Igh intronic enhancer and an Igh-6 constant region gene (of haplotype a) from which the exon encoding the secreted form of Igmu and its associated polyadenylation signal have been deleted.

Allele

Symbol: Ighm^tm1Cgn
Name: targeted mutation 1, University of Cologne
MGI accession ID: MGI:1857187
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ighm
Marker name: immunoglobulin heavy constant mu
Chromosome: 12
Strain of origin: 129S2/SvPas
Molecular note: A neomycin resistance cassette disrupted one of the membrane exons of the gene encoding immunoglobulin heavy chain of the class mu (IgM).