Animal models used in HERV studies. HERV expression is required for normal development and its abnormal activation can result in several cancers and neurological diseases. Transgenic animals are generated by microinjection of DNA fragments or plasmids harboring HERV LTR, env, and rec genes into the pronuclei of fertilized eggs of vertebrate models of zebrafish, rats, and mice, or into the gonad of the worm C. elegans. Regulatory elements of HERV LTRs act as promoters/enhancers in many animal models and can affect the expression of the nearby gene or reporter. Some model animals expressing HERV env and rec genes show the shared features with human diseases such as cancers, ALS, and type-1 diabetes. Transgenic fruit flies expressing human TDP-43 (hTDP-43), which forms pathological aggregates in various neurodegenerative diseases such as ALS, FTD, and AD, activates Drosophila ERV gypsy, that is structurally related to HERV-K, and their neurons degenerate. Genetically modified pigs suppressing porcine endogenous retroviruses (PERVs), which are still infectious, different from HERVs, are developed to overcome a potential risk of cross-species transmission of PERVs in xenotransplantation. Tumor xenograft animal models also show that HERV elements increase cancer cell proliferation and tumor growth. Animal models can be used to analyze the role of HERV function in vivo and help better understand how they are involved in the disease process. Figure was created with BioRender.com.

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