Sugimoto Mayumi, Fujikawa Akira, Womack James E, Sugimoto Yoshikazu
National Livestock Breeding Center, Nishigo, Fukushima 961-8511, Japan.
Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6454-9. doi: 10.1073/pnas.0601015103. Epub 2006 Apr 12.
Mastitis, a mammary gland inflammation in response to bacterial infection, is a major problem in the dairy industry. We found that cows susceptible to mastitis have a three-base insertion in a glycine-coding stretch of the gene for forebrain embryonic zinc finger-like (FEZL), a transcription factor with a role in neuronal development. Mastitis induces FEZL expression in mammary glands, and induced FEZL promotes expression of the axon-attracting molecule semaphorin 5A (SEMA5A) through a GCAG sequence. FEZL also induces SEMA5A expression in susceptible cattle but at a lower level than in resistant cattle. Enhanced SEMA5A induces expression of at least nine genes related to the host's immune response, including TNF-alpha and IL-8. We propose that susceptibility to mastitis results from an impaired immune response due to the lower transcription activity of susceptible FEZL. Our results provide an avenue to select for genetic improvement of resistance to mastitis and suggest that the FEZL-SEMA5A pathway might control both neuronal development and innate immunity.
乳腺炎是一种由细菌感染引起的乳腺炎症，是乳制品行业的一个主要问题。我们发现，易患乳腺炎的奶牛在前脑胚胎锌指样（FEZL）基因的甘氨酸编码区域有一个三碱基插入，FEZL是一种在神经元发育中起作用的转录因子。乳腺炎会诱导乳腺中FEZL的表达，而诱导的FEZL通过GCAG序列促进轴突吸引分子信号素5A（SEMA5A）的表达。FEZL也会在易感牛中诱导SEMA5A的表达，但水平低于抗性牛。增强的SEMA5A会诱导至少九个与宿主免疫反应相关的基因的表达，包括肿瘤坏死因子-α和白细胞介素-8。我们认为，对乳腺炎的易感性是由于易感FEZL的转录活性较低导致免疫反应受损所致。我们的研究结果为选择提高乳腺炎抗性的基因改良提供了一条途径，并表明FEZL-SEMA5A途径可能同时控制神经元发育和先天免疫。
