NOD/ShiLtJ-H2-Ab1^g7-em2Ygch/J

Stock number: 034874
Product name: NOD.Ab^g7-S57D
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

These NOD mice contain a ZFN-mediated knock-in of a serine to aspartic acid mutation at position 57 (S57D) in the MHC class II AΒ chain. These mice are completely resistant to type 1 diabetes (T1D).

Detailed description

NOD.Ab^g7-S57D mice contain a ZFN-mediated mutation targeted to the H2-Ab1 (histocompatibility 2, class II antigen A, beta 1) gene. The serine to aspartic acid mutation at position 57 (S57D) in the MHC class II AΒ chain disrupts the expression of the diabetes susceptible MHC class II I-Ag7 molecule uniquely expressed in NOD mice. I-Ag7 is involved in antigen presentation and T-cell activation, contributing to the development of Insulin-dependent diabetes mellitus (IDDM). NOD.Ab^g7-S57D mice are completely resistant to type 1 diabetes (T1D). The expression level of MHC class II on B cells and dendritic cells is not altered when using a 10-3.6 antibody clone compared to those from wild-type NOD mice. The level of MHC class II staining is lower on B cells and dendritic cells from these mice than those from wild-type NOD mice when AMS-32.1 antibody clone is used, perhaps due to conformational changes of the antibody-binding epitope resulting from the S57D mutation.

Development

This zinc finger nuclease induced mutation targets residue 57 of the H2-Ab1 (histocompatibility 2, class II antigen A, beta 1) gene, resulting in a serine to aspartic acid mutation (S57D) of the MHC class II I-Ag7 molecule. The mRNA encoding the ZFN was injected into NOD/ShiLtJ (Stock No. 001976) one cell embryos and resulting progeny were bred back to NOD/ShiLtJ. Resulting offspring were intercrossed. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize NOD/ShiLtJ oocytes.

Allele

Symbol: H2-Ab1^g7-em2Ygch
Name: endonuclease-mediated mutation 2, Yi-Guang Chen
MGI accession ID: MGI:6391167
Generation method: Endonuclease-mediated
Attributes: Humanized sequence
Synonyms: Ab^g7-S57D; H2-Ab1^em2Ygch
Marker symbol: H2-Ab1
Marker name: histocompatibility 2, class II antigen A, beta 1
Marker synonyms: A beta; Abeta; Bb; CELIAC1; DQB2; H-2Ab; H2-Ab; HLA-DQB; HLA-DQB1; HLA-DXB; I-A^b; Ia2; Ia-2; IAb; I-Abeta; IDDM1; Rmcs1; RT1.B
Chromosome: 17
Strain of origin: NOD/ShiLtJ
Molecular note: The zinc finger nuclease induced mutation targets residue 57 of the gene, resulting in a serine to aspartic acid mutation (S57D). The mutation at position 57 (S57D) in the MHC class II AÃŽÂ’ chain disrupts the expression of the diabetes susceptible MHC class II I-Ag7 molecule uniquely expressed in NOD mice.