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| 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
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| 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.
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| Overall design |
RNASeq data for two pro-B cell subsets (fraction B and CC') isolated from wt and Fnip1-/- mice
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| 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
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| Department |
NIAMS
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| Lab |
biodata mining and discovery section
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| Street address |
10 Center Dr
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| City |
bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (4)
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| 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-/- |
| GSM948903 |
RNASeq of pro-B cell fraction CC', Fnip1-/- |
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| Relations |
| BioProject |
PRJNA168591 |
| SRA |
SRP013758 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE38741_RAW.tar |
385.2 Mb |
(http)(custom) |
TAR (of BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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