Evidence that bovine forebrain embryonic zinc finger-like gene influences immune response associated with mastitis resistance

Abstract

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 SA (SEMASA) through a GCAG sequence. FEZL also induces SEMASA expression in susceptible cattle but at a lower level than in resistant cattle. Enhanced SEMASA induces expression of at least nine genes related to the host's immune response, including TNF-α 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-SEMASA pathway might control both neuronal development and innate immunity. © 2006 by The National Academy of Sciences of the USA.