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Gene mutations in FAR1 cause a rare human disease. Furthermore, altered EL homeostasis has also been associated with various prevalent human diseases. Despite their importance in human health, the exact cellular functions of FAR1 and EL are not well\u2010understood. Here, we report the generation and initial characterization of the first Far1 knockout (KO) mouse model. Far1 KO mice were subviable and displayed growth retardation. The adult KO male mice had smaller testes and were infertile. H&amp;E and immunofluorescent staining showed fewer germ cells in seminiferous tubules. Round spermatids were present but no elongated spermatids or spermatozoa were observed, suggesting a spermatogenesis arrest at this stage. Large multi\u2010nucleated giant cells (MGC) were found lining the lumen of seminiferous tubules with many of them undergoing apoptosis. The immunofluorescent signal of TEX14, an essential component of intercellular bridges (ICB) between developing germ cells, was greatly reduced and mislocalized in KO testis, suggesting the disrupted ICBs as an underlying cause of MGC formation. Integrative analysis of our total testis RNA\u2010sequencing results and published single\u2010cell RNA\u2010sequencing data unveiled cell type\u2010specific molecular alterations underlying the spermatogenesis arrest. Many genes essential for late germ cell development showed dramatic downregulation, whereas genes essential for extracellular matrix dynamics and cell\u2013cell interactions were among the most upregulated genes. Together, this work identified the cell type\u2010specific requirement of ELs in spermatogenesis and suggested a critical role of Far1\/ELs in the formation\/maintenance of ICB during meiosis.<\/jats:p>","DOI":"10.1096\/fj.202201848r","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T10:54:06Z","timestamp":1681210446000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Disrupted intercellular bridges and spermatogenesis in fatty\n                    <scp>acyl\u2010CoA<\/scp>\n                    reductase 1 knockout mice: A new model of\u00a0ether lipid deficiency"],"prefix":"10.1096","volume":"37","author":[{"given":"Bo","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Physiology Wayne State University, School of Medicine  Detroit Michigan 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