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Li et al. Ageing Neur Dis 2022;2:13  https://dx.doi.org/10.20517/and.2022.13     Page 9 of 13

               Table 1. Examples of neurodegenerative disease pigs described in this article
                Pig models               Genes                     Editing type        References
                ALS pig                  SOD1                      TG                  [38]
                ALS pig                  SOD1                      TG                  [9]
                ALS pig                  TDP-43                    TG                  [39]
                HD transgenic pig        HTT                       TG                  [47]
                HD transgenic pig        N-mHTT(105Q)              TG                  [48]
                HD transgenic pig        HTT(1-548)                TG                  [49]
                HD KI pig                HTT                       KI                  [50]
                AD transgenic pig        APPsw                     PM                  [57]
                AD transgenic pig        PSEN1(M146I)              TG                  [58]
                AD transgenic pig        PSEN1, APP                PM                  [59]
                AD transgenic pig        hAPP, hTau, hPS1          PM                  [60]
                PD pig                   PARK7                     KO                  [68]
                PD pig                   PARK2, PINK1              M-KO                [69]
                PD pig                   Parkin, DJ-1, PINK1       M-KO                [70]

               The table lists genes that have been changed using TG, KO, M-KO, PM, or KI. TG: Transgenic; KO: knockout; M-KO: multiplex knockout; KI:
               knock-in; PM: point mutation (by HDR); ALS: amyotrophic lateral sclerosis; HD: Huntington’s disease; AD: Alzheimer’s disease; PD: Parkinson’s
               disease.


               The pig models can also be used for preclinical evaluation of stem cell therapy, gene therapy, and drug
               screening because their body size and metabolism are closer to humans than other species. Their relatively
               fast breeding and reproduction would provide a sufficient number of animals for evaluation of the
               therapeutic effects of drugs and other means. Considering the advanced gene editing tools available, we
               believe that genetically modified pig models will play a more important role in the studies of age-dependent
               neurological diseases in the future.


               DECLARATIONS
               Acknowledgement
               We thank Dr. Xiao-Jiang Li for carefully editing the manuscript.


               Authors’ contributions
               Wrote the review paper: Li C, Li J
               Revised manuscript: Li S, Yan S
               Conceived and designed experiments: Yan S, Lai L
               All authors read and approved the final manuscript.


               Availability of data and materials
               Not applicable.


               Financial support and sponsorship
               This  work  was  supported  by  National  Key  Research  and  Development  Program  of  China
               (2021YFA0805300), The National Natural Science Foundation of China (81922026, 82171244), and
               Guangzhou Key Research Program on Brain Science (202007030008, 202007030003).


               Conflicts of interest
               All authors declared that there are no conflicts of interest.
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