Dog models

Originally described in 1985, hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis (RCND) is a naturally occurring canine kidney cancer syndrome in German shepherd dogs (Lium and Moe, 1985). As the name suggests, RCND is characterised by bilateral, multifocal tumours in the kidney and firm nodules within the skin, thus showing similarity to human BHD syndrome.

The RCND locus was located to a small region on canine chromosome 5 that overlapped with FLCN (Lingaas et al., 2003). The authors described a histidine to arginine mutation (H255R) in exon 7 of canine FLCN that segregated with the disease phenotype and appears to be homozygous lethal (Lingaas et al., 2003).

Researchers also observed a loss of heterozygosity within the renal cysts and tumours of juvenile and adult dogs respectively, indicating a tumour suppressor function for FLCN according to the Knudson two-hit hypothesis (Bønsdorff et al., 2008; Bønsdorff et al., 2009).


Pemberton et al. show that the Weimaraner breed of dog carries a FNIP2 truncating mutation, present at a carrier frequency of 4.285%. Animals carrying biallelic FNIP2 mutations show defective myelination of the spinal cord, which increased over time, although never reached wild type levels. Clinically, these animals develop a tremor phenotype around 12-14 days postpartum, which abates at 3-4 months of age.

The Chow Chow breed of dog is prone to a similar recessive tremor phenotype caused by hypomyelination of the spinal cord. Although direct sequencing was not performed in this breed, cross breeding experiments show that that Chow mutation is likely to be allelic with the Weimaraner mutation, suggesting that a FNIP2 mutation also causes this phenotype in Chows (Pemberton et al., 2013).