Clinical, Biological and Pathological Investigation of Bovine Lymphocyte Intestinal Retention Deficit (BLIRD): a new genetic disorder affecting life expectancy and immunity in Holstein dairy cattle

Abstract

Dozens of missed recessive loci affecting homozygous carriers life expectancy were recently reported. This article details the clinical, biological and pathological manifestations of a new bovine genetic disorder caused by an ITGB7 p.G375S point mutation in the French Holstein cattle breed. Our thorough study involved database analysis of genotyped cattle and a series of case-control investigations of forty homozygous mutants for the causative variant. These mutants had a significantly shorter lifespan (fewer than 64% surviving past three years vs. 87% in controls), along with reduced body weight, daily weight gain, and dairy performance. The mutation did not affect most biochemical parameters, but a marked lymphocytic leucocytosis, moderate eosinophilia and differences in faecal microbiota were observed. Although non-pathognomonic symptoms may be confused with those of common environmental diseases, the blood profile effectively identified suspected carriers who developed ill-thrift and poor growth as heifers. Our research demonstrates that the bovine ITGB7 p.G375S substitution leads to reduced longevity, poor condition and production, in most homozygous carriers. Furthermore, this spontaneous model may help to refine the functions of the {beta}7 integrin in immune homeostasis and defence.