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

Sugimoto, M., Fujikawa, A., Womack, J.E., Sugimoto, Y.
Proceedings of the National Academy of Sciences of the United States of America 2006 v.103 no.17 pp. 6454-6459
cattle, transcription factors, genes, nucleotide sequences, transcription (genetics), gene induction, bovine mastitis, Escherichia coli, lipopolysaccharides, gene expression, messenger RNA, mammary glands, immune response, interleukin-8, tumor necrosis factor-alpha, disease resistance
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.