Tu140 - FAM83H Is Involved in Normal Lymphopoiesis in the Postnatal Hematopoietic Niche

Abstract Text: FAM83H (family with sequence similarity 83 member H) is mostly expressed in epithelial cells and is associated with intracellular transport, cytoskeletal regulation, and enamel formation. Mutations in Fam83h cause amelogenesis imperfecta (AI), characterized by defective enamel. We generated Fam83h knockout (KO) mice using CRISPR/Cas9. While enamel defects were absent, KO mice exhibited reduced body size, scruffy coats, and scaly skin. They developed inflamed front paw lesions, likely caused by a disrupted skin barrier. Elevated neutrophil levels in peripheral blood and impaired leukocyte development, including T, B, and NK cells, were observed in KO mice; however, the soft tissue lesions resolved and returned to normal by 7 weeks of age. Specifically, at two weeks, the thymi of KO mice have reduced capacity to generate T cells, with a partial arrest at the DN stage, and thymic architecture is disturbed. Our findings show that FAM83H primarily expressed by stromal cells, plays a crucial role in modulating lymphoid cell development within postnatal hematopoietic niches. Furthermore, based on our expression data, FAM83H attenuates Wnt signaling by promoting CK1-dependent degradation of β-catenin in postnatal thymic epithelial cells (TECs). These findings highlight FAM83H's vital role in hematopoietic niches and immune cell development.