title: iRhom2 mutation leads to aberrant hair follicle differentiation in mice.
abstract: iRhom1 and iRhom2 are inactive homologues of rhomboid intramembrane serine proteases lacking essential catalytic residues, which are necessary for the maturation of TNFα-converting enzyme (TACE). In addition, iRhoms regulate epidermal growth factor family secretion. The functional significance of iRhom2 during mammalian development is largely unclear. We have identified a spontaneous single gene deletion mutation of iRhom2 in Uncv mice. The iRhom2Uncv/Uncv mice exhibit hairless phenotype in a BALB/c genetic background. In this study, we observed dysplasia hair follicles in iRhom2Uncv/Uncv mice from postnatal day 3. Further examination found decreased hair matrix proliferation and aberrant hair shaft and inner root sheath differentiation in iRhom2Uncv/Uncv mutant hair follicles. iRhom2 is required for the maturation of TACE. Our data demonstrate that iRhom2Uncv cannot induce the maturation of TACE in vitro and the level of mature TACE is also significantly reduced in the skin of iRhom2Uncv/Uncv mice. The activation of Notch1, a substrate of TACE, is disturbed, associated with dramatically down-regulation of Lef1 in iRhom2Uncv/Uncv hair follicle matrix. This study identifies iRhom2 as a novel regulator of hair shaft and inner root sheath differentiation.
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Leilei
authors.affiliation: Institute of JingFeng Medical Laboratory Animal, Beijing 100071, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Bing
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Shaoxia
authors.affiliation: Institute of JingFeng Medical Laboratory Animal, Beijing 100071, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Institute of JingFeng Medical Laboratory Animal, Beijing 100071, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Dongping
authors.affiliation: Institute of JingFeng Medical Laboratory Animal, Beijing 100071, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Huahu
authors.affiliation: Institute of JingFeng Medical Laboratory Animal, Beijing 100071, China.
authors.forename: Shang
authors.initials: S
authors.lastname: Shichen
authors.affiliation: Institute of JingFeng Medical Laboratory Animal, Beijing 100071, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Guangzhou
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Ruiyun
authors.affiliation: Institute of JingFeng Medical Laboratory Animal, Beijing 100071, China.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Institute of JingFeng Medical Laboratory Animal, Beijing 100071, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wenlong
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D057809:HEK293 Cells; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D051881:Receptor, Notch1 / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; C569468:iRhom2 protein, mouse; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse