{"doi":"10.3390/ijms25105299","title":"In the Eyes of the Beholder—New Mertk Knockout Mouse and Re-Evaluation of Phagocytosis versus Anti-Inflammatory Functions of MERTK","abstract":"<jats:p>Greg Lemke’s laboratory was one of the pioneers of research into the TAM family of receptor tyrosine kinases (RTKs). Not only was Tyro3 cloned in his laboratory, but his group also extensively studied mice knocked out for individual or various combinations of the TAM RTKs Tyro3, Axl, and Mertk. Here we primarily focus on one of the paralogs—MERTK. We provide a historical perspective on rodent models of loss of Mertk function and their association with retinal degeneration and blindness. We describe later studies employing mouse genetics and the generation of newer knockout models that point out incongruencies with the inference that loss of MERTK-dependent phagocytosis is sufficient for severe, early-onset photoreceptor degeneration in mice. This discussion is meant to raise awareness with regards to the limitations of the original Mertk knockout mouse model generated using 129 derived embryonic stem cells and carrying 129 derived alleles and the role of these alleles in modifying Mertk knockout phenotypes or even displaying Mertk-independent phenotypes. We also suggest molecular approaches that can further Greg Lemke’s scintillating legacy of dissecting the molecular functions of MERTK—a protein that has been described to function in phagocytosis as well as in the negative regulation of inflammation.</jats:p>","journal":"International Journal of Molecular Sciences","year":2024,"id":623993,"datarank":0.5067732846927138,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.19485705344073828,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.19485705344073828,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":7,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":459485,"name":"Silvia C. 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We provide a historical perspective on rodent models of loss of Mertk function and their association with retinal degeneration and blindness. We describe later studies employing mouse genetics and the generation of newer knockout models that point out incongruencies with the inference that loss of MERTK-dependent phagocytosis is sufficient for severe, early-onset photoreceptor degeneration in mice. This discussion is meant to raise awareness with regards to the limitations of the original Mertk knockout mouse model generated using 129 derived embryonic stem cells and carrying 129 derived alleles and the role of these alleles in modifying Mertk knockout phenotypes or even displaying Mertk-independent phenotypes. We also suggest molecular approaches that can further Greg Lemke’s scintillating legacy of dissecting the molecular functions of MERTK—a protein that has been described to function in phagocytosis as well as in the negative regulation of inflammation.</jats:p>","is_dataset_classified":null,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38791338","pmcid":"PMC11121519","openalex_id":"https://openalex.org/W4396904585","authors":[],"funders":[{"funder_name":"National Eye Institute","grant_id":"1R01EY034003","title":null},{"funder_name":"National Eye Institute","grant_id":"1R21EY033188","title":null},{"funder_name":"National Eye Institute","grant_id":"5R01EY03400202","title":null},{"funder_name":"NEI NIH HHS","grant_id":"R21 EY033188","title":null},{"funder_name":"NEI NIH HHS","grant_id":"R01 EY034003","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R21EY033188-02","title":"Anti-inflammatory role of MerTK in the RPE independent of diurnal outer segment phagocytosis"},{"funder_name":"National Institutes of Health","grant_id":"5R01EY034003-03","title":"Inflammation in MERTK-dependent retinitis pigmentosa"},{"funder_name":"Foundation Fighting Blindness Program Project","grant_id":"","title":null},{"funder_name":"Individual Investigator Research Award from the Foundation Fighting Blindness","grant_id":"","title":null},{"funder_name":"Kim B. and Stephen E. 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