Birt-Hogg-Dube (BHD) syndrome is a rare cancer disorder caused by mutations of the tumor suppressor gene folliculin (Flcn or BHD). BHD manifests in lung (cysts), kidney (polycystic kidney disease and renal cell carcinoma) and skin (fibrofolliculomas), and also exhibits characteristics of ciliopathies. The BHD^flox allele (Flcn^flox) has loxP sites flanking exons 3-4 of the folliculin gene. Mice homozygous for the floxed allele are viable and fertile with no reported abnormalities. When bred to mice that express Cre recombinase, the resulting offspring will have functional FLCN expression deleted in the cre-expressing tissues.

For example, when bred to germline Cre-expressing mice (C57BL/6-congenic CMV-Cre; Stock No. 006054), the resulting global knockout homozygotes die in utero between 3.5-8.5 dpc. Those mice heterozygous for the global null allele (BHD^flox/-) can survive up to two years with some animals developing renal cysts, renal tumors and other neoplasia in other organs.

Flcn^flox mice allow studying cell/tissue-specific FLCN deficiency in the developing kidney (specifically in distal tubules, collecting ducts, and the thick ascending limb of Henle's loop) via breeding with C57BL/6-congenic Ksp-Cre transgenic mice (Stock No. 012237). Such homozygous mice (BHD^flox/flox/Ksp-Cre) develop multiple renal cysts and rapid death; affected animals die in three weeks due to uraemia.

Furthermore, breeding BHD^flox mice to C57BL/6 Sglt2-Cre transgenic mice (Tg(Slc5a2-cre)1Tauc) results in offspring with FLCN deficiency specifically in the renal proximal tubule. Those homozygous mice (Flcn^flox/flox/Sglt2-Cre) develop bilateral cystic kidneys (~50% by 1 month of age), a wide spectrum of kidney tumor subtypes (multiple histological forms) and survival up to two years.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which it was first characterized. The phenotype described above was for BHD^flox mice on a mixed C57BL/6;129 genetic background. It should be noted that the phenotype of C57BL/6-congenic BHD^flox mice could vary from that originally described on the mixed genetic background. We may modify the strain description if necessary as published results become available.