In other species: indicine cattle (zebu)

Categories: Immune system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 600065 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2016

Species-specific description: Some of the resistant cattle described in this entry are genetically-modified organisms (GMO)

Molecular basis: As explained by Shanthalingam et al. (2016), "the signal peptide of CD18 [encoded by ITGB2], an adhesive protein expressed on the surface of leukocytes of cattle and other ruminants, is not cleaved. Intriguingly, leukotoxin produced by Mannheimia haemolytica binds to the intact signal peptide and causes lysis of ruminant leukocytes, resulting in acute pneumonia. In this proof-of-principle study, we used precise gene editing to induce a single amino acid substitution in CD18, which resulted in the cleavage of the signal peptide and abrogation of leukotoxin-induced cytolysis of leukocytes of the gene-edited bovine fetus. This report demonstrates the feasibility of developing lines of cattle genetically resistant to M. haemolytica-caused pneumonia, which will have significant impact on the sustainability of food-animal production in the United States and elsewhere." Workman et al. (2018) reported evidence suggesting "that missense variants in the CD18 signal peptide affect Lkt [a M. haemolytica leukotoxin "that binds to the CD18 receptor on leukocytes, initiates lysis, induces inflammation, and causes acute fibrinous bronchopneumonia"] binding, and animals carrying the C 5 allele may be more susceptible to the effects of Lkt."
Ren et al. (2024) “simultaneously edited three genes in bovine fibroblasts. A knockout of MSTN and PRNP was created and the amino acid Q-G in CD18 was precisely substituted [in the fibroblasts].”

Genetic engineering: Yes - in addition to the occurrence of natural variants, variants have been created artificially, e.g. by genetic engineering or gene editing
Have human generated variants been created, e.g. through genetic engineering and gene editing

Associated gene: