B6.129S2-Cd40lg^tm1Imx/J

Stock number: 002770
Product name: CD40 ligand KO
Research areas: Cancer Research, Immunology, Inflammation and Autoimmunity Research, Mouse/Human Gene Homologs

Description

The CD40L- (or CD154-) knockout mutation is located on the X chromosome. Homozygous females and hemizygous males exhibit humoral immune defects and are a model of human X-linked hyper IgM syndrome.

Detailed description

The CD40L- (or CD154-) knockout mutation is located on the X chromosome. Homozygous females and hemizygous males are viable and fertile. Percentages of B and T cell subpopulations are normal. Homozygous females and hemizygous males exhibit selective deficiencies in humoral immunity (low basal serum isotype levels and undetectable IgE) as well as abnormal secondary antigen-specific responses to immunization with a thymus-dependent antigen. The phenotype of the mice resembles human X-linked hyper IgM syndrome.

Development

The CD40L- (or CD154-) knockout mutation was designed by Jacques Peschon (Immunex) to replace exons 3 and 4 of the CD40 ligand gene (Cd40lg) on the X chromosome with a PGKneo cassette. The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting male chimeric animals were crossed to C57BL/6 female mice. Heterozygous (129/SV x C57BL/6)F1 females were crossed to C57BL/6 males to generate hemizygous males. CD40L- mice were subsequently backcrossed on to the C57BL/6J background for five generations and then donated to The Jackson Laboratory Repository in 1995 as Stock No. 002770. The mice are maintained on a C57BL/6J genetic background.

Allele

Symbol: Cd40lg^tm1Imx
Name: targeted mutation 1, Immunex
MGI accession ID: MGI:1857145
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Cd40lg
Marker name: CD40 ligand
Chromosome: X
Strain of origin: 129S2/SvPas
Molecular note: Exons 3 and 4 were replaced with a neomycin cassette. Homozygous mutant animals fail to express functional protein on the cell surface.