title: A novel role of RASSF9 in maintaining epidermal homeostasis.
abstract: The physiological role of RASSF9, a member of the Ras-association domain family (RASSF), is currently unclear. Here, we report a mouse line in which an Epstein-Barr virus Latent Membrane Protein 1 (LMP1) transgene insertion has created a 7.2-kb chromosomal deletion, which abolished RASSF9 gene expression. The RASSF9-null mice exhibited interesting phenotypes that resembled human ageing, including growth retardation, short lifespan, less subcutaneous adipose layer and alopecia. In the wild-type mice, RASSF9 is predominantly expressed in the epidermal keratinocytes of skin, as determined by quantitative reverse-transcription PCR, immunofluorescence and in situ hybridization. In contrast, RASSF9-/- mice presented a dramatic change in epithelial organization of skin with increased proliferation and aberrant differentiation as detected by bromodeoxyuridine incorporation assays and immunofluorescence analyses. Furthermore, characteristic functions of RASSF9-/- versus wild type (WT) mouse primary keratinocytes showed significant proliferation linked to a reduction of p21Cip1 expression under growth or early differentiation conditions. Additionally, in RASSF9-/- keratinocytes there was a drastic down-modulation of terminal differentiation markers, which could be rescued by infection with a recombinant adenovirus, Adv/HA-RASSF9. Our results indicate a novel and significant role of RASSF9 in epidermal homeostasis.
authors: Department of Medical Research and Development, Chang Gung Memorial Hospital at Lin-Kou, Taoyuan, Taiwan. lcm5132@mail.cgu.edu.tw
authors: Chiou-Mei
authors: CM
authors: Lee
authors: Polung
authors: P
authors: Yang
authors: Lih-Chyang
authors: LC
authors: Chen
authors: Chia-Chun
authors: CC
authors: Chen
authors: Shinn-Chih
authors: SC
authors: Wu
authors: Hsiao-Yun
authors: HY
authors: Cheng
authors: Yu-Sun
authors: YS
authors: Chang
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004817:Epidermis / Q000502:physiology*; D020869:Gene Expression Profiling; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033921:Vesicular Transport Proteins / Q000502:physiology*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C116429:RASSF9 protein, human; D033921:Vesicular Transport Proteins