Information on all the BHD models can be found in: What is BHD?- Cell Lines and Model Organisms
Nihon Rat Model:
This experimental model contains a cytosine insertion within exon 3 of the FLCN gene in rat chromosome 10. This results in a frame shift and premature stop codon, which is similar to that observed in BHD syndrome in humans (Okimoto et al., 2004).
To obtain the Nihon rat, please contact Kazuo Okimoto directly (of Dainippon Sumitomo Pharma Company Ltd., Osaka, Japan).
More detailed information can be found in: What is BHD? – Rat model
Mouse Models:
Several mouse models have been generated:
| Description | Additional Information | Observations | Reference/Source |
| Kidney-specific FLCN knockout | Cre-lox deletion of exon 7. (Ksp-Cre) | Development of polycystic kidneys, renal failure and death within 3 weeks after birth. | Baba et al., 2008 (National Cancer Institute, Bethesda, USA) |
| Kidney-specific FLCN knockout
Kidney proximal tube-specific knockout |
Cre-lox deletion of exons 3 and 4. (Ksp-Cre)
(Sglt2-Cre) |
Development of polycystic kidneys, renal failure and death within 3 weeks after birth.
High penetrance development of renal cysts ≈1 month and mixes histology tumours ≈6 months. Death in under 2 years. Heterozygotes show low tumourigenicity. |
Chen et al., 2008 (Van Andel Research Institute, Michigan, USA)
(University of Rochester Medical Centre, USA) |
| Heterozygous gene trap FLCN knockout | β-geo insertion between exons 8 and 9. | Development of renal cysts and neoplasia ≈3-6 months after birth. | Hartman et al., 2009 (Brigham and Women’s Hospital, Boston, USA) |
| Heterozygous FLCN knockout | Cre-lox deletion of exon 7. | Development of renal cysts and solid tumours ≈10 months after birth. FLCN homozygous null mice die from embryonic day (E) 5.5 to E6.5. | Hasumi et al., 2009 (National Cancer Institute, Bethesda, USA) |
| Heterozygous gene trap FLCN knockout | β-geo insertion between exons 8 and 9. | Development of renal cysts and tumours ≈6 months after birth. FLCN homozygous null mice die before E8.5. | Hudon et al., 2010 (McGill University, Montréal, Québec) |
| Heterozygous gene trap FLCN knockout | β-geo insertion between exons 8 and 9. | Strong FLCN expression in the yolk sac visceral endoderm at E10.5. FLCN homozygous null mice die from E7.5. | Cash et al., 2011 (University of Pennsylvania, Philadelphia, USA) |
More detailed information regarding each of these mouse models can be found in: What is BHD? – Mouse models
Dog Model:
Folliculin has been identified as the mutated gene in a condition known as Hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis (RCND) in German shepherd dogs at the Norwegian School of Veterinary Science, Oslo (Lingaas et al., 2003).
More detailed information can be found in: What is BHD? – Dog model
Drosphila Model:
RNA interference against FLCN was used at the National Cancer Institute in Frederick, USA, to achieve an altered phenotype in Drosophila (Singh et al., 2006).
More detailed information can be found in: What is BHD? – Drosophila model
Zebrafish Model:
A zebrafish model of BHD syndrome is being developed by Dr Ferenc Mueller at the University of Birmingham Medical School, UK. This work is being funded by the Myrovlytis Trust.
Further reading: all literature relating to this information, plus more, can be found in the BHD Literature Database.