B6.129P2-H2-K1^tm1Bpe H2-D1^tm1Bpe/DcrJ

Stock number: 019995
Product name: double H2K^bD^b knockout
Research areas: Immunology, Inflammation and Autoimmunity Research, Neurobiology Research, Research Tools, Virology Research

Description

These double H2K^bD^b KO mice carry knockout alleles of the MHC class I genes and exhibit decreased susceptibility to viral infection, as well as enhanced motor learning. They are suitable for use in applications related to the study of adaptive immunity, cytoxic T cell response and cerebellar synaptic plasticity.

Detailed description

These H-2 K^bD^b knock-out mice carry knock-out alleles of the MHC class I genes (K^b null and D^b null) and lack CD8+ TCRalpha/beta T-cells, but have more CD4-positive, alpha beta T cells, and fewer single positive CD8 peripheral T-cells. Mice homozygous for both alleles exhibit diminished innate immune response, have decreased susceptibility to Lymphocytic Choriomeningitis Virus infection, and have an increased cytoxic T cell response to Listeria monocytogenes infection. These mutant mice exhibit enhanced motor learning, with lowered threshold for induction of long-term depression at parallel fiber- Purkinje cell synapses.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

The H2-K1^tm1Bpe knockout allele (K^b null) and H2-D1^tm1Bpe knockout allele (D^b null) were both created by Dr. Beatrice Perarnau (Institut Pasteur, Paris France).
The K^b null allele has a hypoxanthine phosphoribosyl transferase (HPRT) minigene in the opposite transcriptional orientation replacing the second and third exons (which encode the α1-α2 peptide-presenting domains) of the H2-K^b locus (H2-K1) on chromosome 17. The construct was electroporated into 129P2/OlaHsd-Hprt^b-m3-derived E14TG2a embryonic stem (ES) cells. Mutant animals were outcrossed to C57BL/6J. K^b null animals on a mixed B6;129 genetic background were used as described below.
The D^b null allele has a lacZ gene and a neomycin resistance gene replacing the first three exons of the H2-D^b locus (H2-D1) on chromosome 17. The construct was electroporated into 129P2/OlaHsd-derived CGR-8 embryonic ES cells. Mutant animals were outcrossed to C57BL/6J. The D^b null animals on a mixed B6;129 genetic background were bred to B6;129-K^b null mice to generate the B6;129-D^b K^b double knockout line.
Dr. Derry Roopenian obtained double knock-out mice that had been backcrossed to C57BL/6 for 9 generations, and then further backcrossed the mice to N11 on C57BL/6J. The mice were then maintained as double homozygotes before being cryopreserved as sperm. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: H2-K1^tm1Bpe
Name: targeted mutation 1, Beatrice Perarnau
MGI accession ID: MGI:1931444
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: H2-K1
Marker name: histocompatibility 2, K1, K region
Chromosome: 17
Strain of origin: 129P2/OlaHsd
Molecular note: The central part of the H2-K gene, including the second and third exons was replaced by a HPRT minigene.

Allele

Symbol: H2-D1^tm1Bpe
Name: targeted mutation 1, Beatrice Perarnau
MGI accession ID: MGI:1931445
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: H2-D1
Marker name: histocompatibility 2, D region locus 1
Chromosome: 17
Strain of origin: 129P2/OlaHsd
Molecular note: Exons 1, 2 and 3 of the b haplotype gene were replaced with plasmid sequences and a neomycin cassette.