Construction of SARM1 conditional knockout mice in nervous system and its application
XIANG Ludan1, SUN Huankun1, WU Qian1, WANG Wei1, HUANG Zhihui2, YU Xin1
1.School of Mental Health, Wenzhou Medical University, Wenzhou 325035, China; 2.Institute of Holistic Pharmacy, Hangzhou Normal University, Hangzhou 311121, China
XIANG Ludan,SUN Huankun,WU Qian, et al. Construction of SARM1 conditional knockout mice in nervous system and its application[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2021, 51(4): 259-265.
Abstract：Objective: To construct neuronal-specific conditional SARM1 knockout mice and to provide a research tool for exploring the function of SARM1 in the nervous system. Methods: SARM1flox/flox transgenic mice were generated by using embryonic stem (ES) cell targeting technology. Next SARM1flox/flox transgenic mice were crossed with Nestin-Cre transgenic mouse to generate neuronal-specific conditional SARM1 knockout mice. After that the conditional SARM1 KO mice were genotyped by using polymerase chain reaction (PCR). Western blot was performed to confirm the loss of SARM1 protein in the brain tissues of these mice. Behavior tests such as open field and elevated plus maze test were performed to assess any emotional behavior and general anxiety level in these mice. Results: SARM1 protein was highly expressed in the central nervous system, which was mainly expressed in neurons. Genotyping results revealed that neuronal-specific conditional SARM1 knockout
mice were successfully generated. Further more, compared with wild type mice, SARM1 protein level was significantly decreased in brain tissues of SARM1Nestin-CKO mice (P<0.05). Conditional knockout of SARM1 gene in central nervous system did not affect the growth and development of mice, or the general morphology of brain tissue and the number of neuronal cells. Meanwhile, these mice had no obvious anxiety disorder phenotype. Conclusion: We have successfully generated a mouse line that specifically knocks out the SARM1 gene in neuronal cells. The application of this mutant mouse line may provide a useful tool for exploring the role of SARM1 gene in neuropsychiatric diseases and neurodegenerative diseases.
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