OMIA:002073-9913 : Resistance/susceptibility to Mannheimia haemolytica leukotoxin in Bos taurus
Categories: Immune system phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 600065 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: unknown
Key variant known: yes
Year key variant first reported: 2016
Species-specific description: 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."
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|ITGB2||integrin subunit beta 2||Bos taurus||1||NC_037328.1 (144788839..144759539)||ITGB2||Homologene, Ensembl , NCBI gene|
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2018||Workman, A.M., Chitko-McKown, C.G., Smith, T.P.L., Bennett, G.L., Kalbfleisch, T.S., Basnayake, V., Heaton, M.P. :|
|A bovine CD18 signal peptide variant with increased binding activity to <i>Mannheimia hemolytica</i> leukotoxin. F1000Res 7:1985, 2018. Pubmed reference: 30881690 . DOI: 10.12688/f1000research.17187.1.|
|2016||Shanthalingam, S., Tibary, A., Beever, J.E., Kasinathan, P., Brown, W.C., Srikumaran, S. :|
|Precise gene editing paves the way for derivation of Mannheimia haemolytica leukotoxin-resistant cattle. Proc Natl Acad Sci U S A :, 2016. Pubmed reference: 27799556 . DOI: 10.1073/pnas.1613428113.|
- Created by Frank Nicholas on 09 Nov 2016
- Changed by Frank Nicholas on 09 Nov 2016
- Changed by Frank Nicholas on 18 Sep 2019
- Changed by Frank Nicholas on 15 May 2020