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A study from scientists in the Ministry of Agriculture in Northwest A&F University, Yangling, China has described production of a herd of genetically engineered cattle with improved resistance to low levels of bovine tuberculosis (TB) infection. The study was published last week in the journal Proceedings of the National Academy of Sciences. The study authors commented: "Our results contribute to the control and prevention of bovine tuberculosis and provide a previously unidentified insight into breeding animals for disease resistance."

Bovine TB is a risk in many parts of the world, including the UK, New Zealand and parts of Africa and Asia. It led to culling of over 26,000 cattle in the UK alone in 2013. It is a chronic infectious disease which affects a broad range of mammalian hosts and is considered a particularly serious threat to agriculture in many less-developed countries.

In the current study, the research team used a genetic engineering system called the transcription activator-like effector nickase (TALEN) system. This enabled them to introduce a mouse gene called SP110 to a specific location in the bovine genome in Holstein–Friesian cattle. Polymorphisms in SP110 have been associated with risk of developing TB in mice, humans and cattle. The results indicated that this modification produced tuberculosis-resistant cattle. Results of both in vitro and in vivo experiments suggested that the transgenic cattle were able to control the growth and multiplication of Mycobacterium bovis, kill the bacteria via apoptosis after infection, and efficiently resist low dose infection with M. bovis transmitted from tuberculous cattle in nature. Use of the TALEN system to ‘knock in’ the mouse SP110 gene thus resulted in a heritable genome modification which was facilitative of TB resistance.

Prof Heiner Niemann, of the Institute of Farm Animal Genetics at Friedrich-Loeffler-Institut, Germany, said that the findings of the study were another step towards the creation of disease resistant livestock animals based on advanced genetic tools. However, he cautioned: "Whether this approach protects cows against TB infection when exposed to high doses of the pathogen remains to be determined."

References:
Wu H et al. (2015). TALE nickase-mediated SP110 knockin endows cattle with increased resistance to tuberculosis. PNAS doi: 10.1073/pnas.1421587112
Ruiz-Larranaga O et al. (2010).  SP110 as a novel susceptibility gene for Mycobacterium avium subspecies paratuberculosis infection in cattle. Journal of Dairy Science 93(12):5950-8. DOI: 10.3168/jds.2010-3340