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.
Dr. Jacques Peschon, Amgen
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.
Of note, CD40L- animals backcrossed onto the C57BL/6J background are available as Stock No. 002770.
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 on a mixed C57BL;129S genetic background were donated to The Jackson Laboratory Repository in 1995 as Stock No. 002428. Upon arrival, mice were bred to B6129SF1/J animals (Stock No. 101043) for a least one generation. The mice are maintained on a mixed C57BL/6;129S genetic background.
|Allele Name||targeted mutation 1, Immunex|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||CD154-; CD40L-; CD40LKO; Tnfsf5tm1Imx|
|Gene Symbol and Name||Cd40lg, CD40 ligand|
|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.|
|Mutations Made By|| |
Dr. Jacques Peschon, Amgen
The CD40L- (or CD154-) knockout mutation is located on the X chromosome. Homozygous females and hemizygous males are viable and fertile. When maintaining a live colony, homozygous females may be bred to hemizygous males. Sex ratios among offspring are normal. Expected coat colors from breeding is black and white bellied agouti.
Homozygous females and hemizygous males are somewhat immunodeficient. As such, and similar to other immunodeficient strains, maintenance in high health status (specific pathogen-free) vivaria promotes overall colony health. If CD40L-deficient homozygous mice are maintained in low health barrier rooms, the use of medicated water (e.g., sulfatrim/trimethoprim-sulfa or enrofloxacin/Baytril) may be needed to increase overall colony health.
When using the CD40 ligand KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #002428 in your Materials and Methods section.