NOD.B6-Mcph1^{Tg(HLA-A2.1)1Enge}/DvsJ

Stock number: 005512
Product name: NOD.HLA-A2.1
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

These transgenic mice express the human MHC class I HLA-A2.1 molecule.

Detailed description

Homozygous mice carrying the (HLA-A2.1)1Enge transgene ubiquitously express significant quantities of the human MHC class I HLA-A2.1 molecules. These HLA-A2.1 molecules mediate beta cell auto-reactive CD8 T cell responses that when added to those elicited by endogenous murine MHC class I variants results in a significantly accelerated rate of diabetes onset in either the hemizygote or homozygote transgenic mouse when compared to NOD/Lt controls (Marron et al., 2002). The transgene integrated into chromosome 8 causing a duplication in Mcph1 (microcephaly, primary autosomal recessive 1). The duplication results in a functional knock-out of Mcph1 in homozygous mice.

This model is useful for studying the role of MHC class I molecules in Type 1 Diabetes.

Development

Using marker assisted analysis for all known Idd loci, the transgenic allele HLA-A2.1 from C57BL/6-Tg(HLA-A2.1)1Enge/J (stock# 3088) was backcrossed 10 generations to NOD/Lt prior to making homozygote (Marron et al., 2002). In 2005, the Type 1 Diabetes Resource received NOD.B6-Tg(HLA-A2.1)1Enge/Dvs at N10F34. The Tg(HLA-A2.1)1Enge transgene integrated into chromosome 8 causing a duplication in Mcph1 (microcephaly, primary autosomal recessive 1).

Allele

Symbol: Mcph1^{Tg(HLA-A2.1)1Enge}
Name: transgene insertion 1, Victor H Engelhard
MGI accession ID: MGI:3056375
Generation method: Transgenic
Attributes: Null/Knockout; Inserted expressed sequence; Humanized sequence
Marker symbol: Mcph1
Marker name: microcephaly, primary autosomal recessive 1
Chromosome: 8
Strain of origin: C57BL/6
Expressed genes: HLA-A,major histocompatibility complex, class I, A,human
Molecular note: The transgene contains the full length HLA-A2.1 gene. Expression of human class I MHC Ag HLA-A2.1 was detected on cells from homozygous transgenic spleen, bone marrow, and thymus. Line 1 inserted into the gene at 18736683-18757058 (Build GRCm38/mm10) resulting in a duplication. The duplication results in a functional knock-out. Founder line 1 has a copy number of 3-8.
General note: Expression of this human class I molecule in transgenic mice does not result in expansion of the number of cytotoxic T lymphocyte (CTL) precursors specific for other human class I Ag, HLA-B27 or HLA-A2.2.