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Series GSE38741 Query DataSets for GSE38741
Status Public on Jun 16, 2012
Title The Folliculin-Fnip1 pathway deleted in human Birt-Hogg-Dube syndrome is required for B cell development.
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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
Contributor(s) Baba M, Keller JR, Sun H, Resch W, Kuchen S, Suh H, Hasumi H, Hasumi Y, Kieffer-Kwon K, Gallego Gonzalez C, Hughes RM, Klein ME, Bible P, Schmidt LS, Linehan M, Casellas R
Citation(s) 22709692
Submission date Jun 15, 2012
Last update date May 15, 2019
Contact name Seolkyoung Jung
Organization name NIH
Department NIAMS
Lab biodata mining and discovery section
Street address 10 Center Dr
City bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (4)
GSM948900 RNASeq of pro-B cell fraction B, wt
GSM948901 RNASeq of pro-B cell fraction CC', wt
GSM948902 RNASeq of pro-B cell fraction B, Fnip1-/-
BioProject PRJNA168591
SRA SRP013758

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Supplementary file Size Download File type/resource
GSE38741_RAW.tar 385.2 Mb (http)(custom) TAR (of BEDGRAPH)
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Raw data are available in SRA
Processed data provided as supplementary file

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