Bovine Lymphocyte Intestinal Retention Defect (BLIRD): a novel recessive immunogenetic disorder in Holstein cattle

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 the ITGB7 p.G375S point mutation in the French Holstein cattle breed (BLIRD: OMIA:002872–9913). Our thorough study involved database analysis of genotyped cattle and a series of case-control investigations of forty individuals homozygous for the causative variant. These variant homozygotes had a significantly shorter lifespan (fewer than 64% surviving past three years vs. 87% in control), 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 integrin β7 (ITGB7) in immune homeostasis and defence.近期已有研究报道了数十个可影响纯合携带者预期寿命的隐性基因座。本文详细阐述了法国荷斯坦牛中由ITGB7基因p.G375S点突变引发的新型牛遗传疾病（BLIRD: OMIA:002872–9913）的临床、生物学及病理学表现。本研究通过对已完成基因型分型牛只的数据库分析，以及针对40例携带该致病变异的纯合个体开展的系列病例对照调查，完成了全面深入的探究。此类变异纯合子的寿命显著缩短：3岁以上存活率仅64%以下，而对照组同期存活率达87%；同时其体重、日增重及泌乳性能均有所下降。该突变并未对多数生化指标产生显著影响，但可引发明显的淋巴细胞性白细胞增多症、中度嗜酸性粒细胞增多症以及粪便微生物群的改变。尽管非特异性症状易与常见环境性疾病相混淆，但通过血液检测指标可有效识别出表现为青年母牛生长迟缓、体况不佳的疑似携带者。本研究证实，牛ITGB7基因p.G375S突变可导致绝大多数纯合携带者寿命缩短、体况不良及生产性能下降。此外，该自发疾病模型可为解析整合素β7（integrin β7）在免疫稳态与机体防御中的功能提供重要的研究载体。