ArticleJournal of the National Cancer Institute2008
Kidney-targeted Birt-Hogg-Dube gene inactivation in a mouse model: Erk1/2 and Akt-mTOR activation, cell hyperproliferation, and polycystic kidneys.
Article in Journal of the National Cancer Institute, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 1 of them a synthesis that pooled it.
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Who cites it
147 citing papers in PubMed, 1 synthesis or guideline pooled it, 255 citations in OpenAlex.
- ERN GENTURIS clinical practice guidelines for the diagnosis, surveillance and management of people with Birt-Hogg-Dubé syndrome.European journal of human genetics : EJHG · 2024Guideline
- Trial
- Birt-Hogg-Dubé syndrome.Nature reviews. Disease primers · 2026Review
- Synergistic role of TFEB/TFE3 and mTORC1 in kidney cystogenesis and tumorigenesis.Cell death and differentiation · 2026Article
- Hyperactivation of mTORC1 signaling mediates folliculin deficiency-induced pulmonary cyst formation in Birt-Hogg-Dubé syndrome.The Journal of clinical investigation · 2026Article
- Substrate-selective mTORC1 regulation and gene dosage-dependent tissue divergence in Birt-Hogg-Dubé syndrome.Frontiers in oncology · 2026Review
- FLCN loss is characterized by SQSTM1/p62 accumulation despite functional autophagy flux in Birt-Hogg-Dubé syndrome-associated kidney cancer.Autophagy reports · 2026Article
- Comparative transcriptome atlas as an assistive modality for complex classification of rare kidney cancers.Nature communications · 2025Article
- SFPQ-TFE3 reciprocally regulates mTORC1 and induces lineage plasticity in a mouse model of renal tumorigenesis.Nature communications · 2025Article
- Folliculin Deletion in the Mouse Kidney Results in Cystogenesis of the Loops of Henle via Aberrant TFEB Activation.The American journal of pathology · 2025Article
- Folliculin depletion results in liver cell damage and cholangiocarcinoma through MiT/TFE activation.Cell death and differentiation · 2025Article
- Differential Diagnosis and a Novel Mutation in Birt-Hogg-Dubé Syndrome: Insights from 2 Cases.The American journal of case reports · 2025Article
- mTOR pathway diseases: challenges and opportunities from bench to bedside and the mTOR node.Orphanet journal of rare diseases · 2025Review
- Unveiling the Genetic Puzzle: Asymmetric Hypertrophy in a Heart Transplant Recipient Linked to Birt-Hogg-Dubé Syndrome.Arquivos brasileiros de cardiologia · 2025Article
- A novel uORF regulates folliculin to promote cell growth and lysosomal biogenesis during cardiac stress.Scientific reports · 2025Article
- Targeting amino acid metabolism to inhibit gastric cancer progression and promote anti-tumor immunity: a review.Frontiers in immunology · 2025Review
- CRISPR screens unveil nutrient-dependent lysosomal and mitochondrial nodes impacting intestinal tissue-resident memory CD8Immunity · 2024Article
- The Spectrum of Renal "TFEopathies": Flipping the mTOR Switch in Renal Tumorigenesis.Physiology (Bethesda, Md.) · 2024Review
- Review
- Metabolic alterations in hereditary and sporadic renal cell carcinoma.Nature reviews. Nephrology · 2024Review
87 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundPatients with Birt-Hogg-Dubé (BHD) syndrome harbor germline mutations in the BHD tumor suppressor gene that are associated with an increased risk for kidney cancer. BHD encodes folliculin, a protein that may interact with the energy- and nutrient-sensing 5'-AMP-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) signaling pathways.
methodsWe used recombineering methods to generate mice with a conditional BHD allele and introduced the cadherin 16 (KSP)-Cre transgene to target BHD inactivation to the kidney. Kidney cell proliferation was measured by BrdU incorporation and phospho-histone H3 staining. Kidney weight data were analyzed with Wilcoxon's rank-sum, Student's t, and Welch's t tests. Hematoxylin and eosin staining and immunoblot analysis and immunohistochemistry of cell cycle and signaling proteins were performed on mouse kidney cells and tissues. BHD knockout mice and kidney cells isolated from BHD knockout and control mice were treated with the mTOR inhibitor rapamycin. Mouse survival was evaluated by Kaplan-Meier analyses. All statistical tests were two-sided.
resultsBHD knockout mice developed enlarged polycystic kidneys and died from renal failure by 3 weeks of age. Targeted BHD knockout led to the activation of Raf-extracellular signal-regulated protein kinase (Erk)1/2 and Akt-mTOR pathways in the kidneys and increased expression of cell cycle proteins and cell proliferation. Rapamycin-treated BHD knockout mice had smaller kidneys than buffer-treated BHD knockout mice had (n = 4-6 mice per group, relative kidney/body weight ratios, mean = 4.64% vs 12.2%, difference = 7.6%, 95% confidence interval = 5.2% to 10.0%; P < .001) and longer median survival time (n = 4-5 mice per group, 41.5 vs 23 days; P = .0065 ).
conclusionsHomozygous loss of BHD may initiate renal tumorigenesis in the mouse. The conditional BHD knockout mouse may be a useful research model for dissecting multistep kidney carcinogenesis, and rapamycin may be considered as a potential treatment for Birt-Hogg-Dubé syndrome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.