RRC ID 5315
Author Yabe D, Fukuda H, Aoki M, Yamada S, Takebayashi S, Shinkura R, Yamamoto N, Honjo T.
Title Generation of a conditional knockout allele for mammalian Spen protein Mint/SHARP.
Journal Genesis
Abstract The Spen protein family is found in worms, flies, and mammals, and is implicated in diverse biological processes from embryogenesis to aging. Spen proteins have three N-terminal RNA recognition motifs and a C-terminal SPOC domain. The mammalian Spen proteins Mint and its human ortholog SHARP interact with the Notch-signaling mediator RBP-J as well as Msx2 and several unliganded nuclear hormone receptors, and impart transcription-repressing activity to these molecules by recruiting corepressors through the SPOC domain. Despite these in vitro findings, Mint/SHARP's physiological role is largely unknown, because Mint germline knockouts are embryonic lethal. To analyze Mint/SHARP function in postnatal mice, we created Mint-floxed mice that allow the Cre/loxP-mediated conditional knockout of Mint. We analyzed Mint and RBP-J epistasis during Notch-dependent splenic B-lymphocyte development, and found that Mint suppresses Notch signaling through RBP-J. In addition, Mint deficiency caused severe hypoplasia in postnatal brain, suggesting it may regulate neuronal cell survival.
Volume 45(5)
Pages 300-6
Published 2007-5
DOI 10.1002/dvg.20296
PMID 17457934
MeSH Animals B-Lymphocytes / cytology B-Lymphocytes / metabolism Brain / metabolism Brain / pathology DNA-Binding Proteins / metabolism Gene Targeting / methods Homeodomain Proteins / genetics Humans In Situ Hybridization Mice Mice, Inbred C57BL Mice, Inbred CBA Mice, Knockout Mice, Transgenic Nuclear Proteins / deficiency* Nuclear Proteins / genetics* Nuclear Proteins / metabolism Receptors, Notch / metabolism Signal Transduction
IF 2.667
Times Cited 16