TALE nickase-mediated SP110 knockin endows cattle with increased resistance to tuberculosis.
Transcription activator-like effector nuclease (TALEN)-mediated genome modification has been applied successfully to create transgenic animals in various species, such as mouse, pig, and even monkey. However, transgenic cattle with gene knockin have yet to be created using TALENs. Here, we report site-specific knockin of the transcription activator-like effector (TALE) nickase-mediated SP110 nuclear body protein gene (SP110) via homologous recombination to produce tuberculosis-resistant cattle. In vitro and in vivo challenge and transmission experiments proved that the transgenic cattle are able to control the growth and multiplication of Mycobacterium bovis, turn on the apoptotic pathway of cell death instead of necrosis after infection, and efficiently resist the low dose of M. bovis transmitted from tuberculous cattle in nature. In this study, we developed TALE nickases to modify the genome of Holstein-Friesian cattle, thereby engineering a heritable genome modification that facilitates resistance to tuberculosis.
College of Veterinary Medicine and Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China.
Haibo
H
Wu
College of Veterinary Medicine and Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China.
Yongsheng
Y
Wang
College of Veterinary Medicine and Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China.
Yan
Y
Zhang
College of Veterinary Medicine and.
Mingqi
M
Yang
Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China.
Jiaxing
J
Lv
College of Veterinary Medicine and Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China.
Jun
J
Liu
College of Veterinary Medicine and Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China zhy1956@263.net.
Yong
Y
Zhang
D000818:Animals; D017209:Apoptosis; D002417:Cattle; D053904:DNA Breaks, Single-Stranded; D003850:Deoxyribonuclease I / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D055879:Gene Knock-In Techniques; D018014:Gene Transfer Techniques; D016678:Genome; D057809:HEK293 Cells; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D015778:Minor Histocompatibility Antigens; D009163:Mycobacterium bovis; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D014158:Transcription, Genetic; D014380:Tuberculosis, Bovine / Q000235:genetics* / Q000382:microbiology / Q000517:prevention & control*
D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; C555439:SP110 protein, bovine; C000598498:Sp110 protein, mouse; D004720:Endonucleases; D003850:Deoxyribonuclease I
TALEN; disease resistance; homologous recombination; single-strand break; tuberculosis