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Title: The Folliculin-Fnip1 pathway deleted in human Birt-Hogg-Dube syndrome is required for B cell development.      
keywords:
Transcriptome or Gene expression
ID:
PRJNA168591
description:
Birt-Hogg-Dube (BHD) syndrome is an autosomal dominant disorder characterized by hamartomas of skin follicles, cystic lung disease, and renal neoplasia. Affected individuals carry heterozygous mutations in Folliculin (FLCN), a tumor suppressor gene that becomes biallelically inactivated in kidney tumors by second-hit mutations. Similar to other factors implicated in kidney malignancies, Folliculin has been shown to modulate activation of mammalian target of rapamycin (mTOR). However, its precise in vivo function is largely unknown because germline deletion of Flcn results in early embryonic lethality in animal models. We here describe mice deficient in the newly characterized Folliculin-Interacting Protein 1 (Fnip1). In contrast to Flcn, Fnip1-/- mice develop normally, are not susceptible to kidney neoplasia, but display a striking pro-B cell block that is independent of mTOR activity. We show that this developmental arrest results at least in part from impaired V(D)J recombination and caspase-induced cell death, and that pre-recombined V(D)J and Bcl2 transgenes reconstitute pre-B and mature B cell populations respectively. We also demonstrate that conditional deletion of Flcn recapitulates the pro-B cell arrest of Fnip1-/- mice. Our studies thus demonstrate that the Flcn-Fnip complex deregulated in BHD syndrome is absolutely required for B cell differentiation and that it functions both through mTOR dependent and independent pathways. Overall design: RNASeq data for two pro-B cell subsets (fraction B and CC') isolated from wt and Fnip1-/- mice
accesstypes:
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA168591
authentication:
none
authorization:
none
ID:
pmid:22709692
dateReleased:
06-16-2012
name:
Mus musculus
ncbiID:
ncbitax:10090
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject
  • HHSN261200800001C/RC/CCR NIH HHS/United States

  • HHSN261200800001E/CA/NCI NIH HHS/United States

  • Z01 BC011028-01/ImNIH/Intramural NIH HHS/United States

  • Z01 BC011043-01/ImNIH/Intramural NIH HHS/United States

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