Renal Dysplasia

 

Gene: CLDN16

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease. Both parents of an affected animal must be carriers of at least one copy of the mutation. Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

Mutation Type 1 : Deletion, CLDN16 gene; deletion of 37kb exon1 to exon4, chr.1.

Mutation Type 2 : Deletion CLDN16 gene; deletion of 56kb, exon1 to exon4 plus 21 pb exon5, chr.1.

Medical systems: Urinary, blood

Breeds: Japanese Black (Wagyu)

Age of onset of symptoms: Between 2 and 5 months.

A genetic disease of renal tubular dysplasia involving chronic interstitial nephritis is described in the Japanese Black (Wagyu) cattle breed. Clinical signs include low birth weight, poor growth, renal failure with frequent urination and long hooves.  Affected animals have an increased respiration rate due to metabolic acidosis and show increased levels of blood urea nitrogen, creatinine and inorganic phosphorus. Disease progression is variable but death due to renal failure can occur before 6 months of age.  Histopathology of kidneys from affected animals showed renal tubular dysplasia with fibrosis.  Molecular studies revealed large deletions in bovine chromosome 1 that affectively ablate the CLDN16 gene.   The CLDN16 gene codes for a claudin protein involved in tight junction formation in renal tubules.  The ablation of the CLDN16 gene results in defective renal tight junctions and failure of glomerular filtration and tubular resorption.  A 1995 study of 385 Wagyu animals recorded 17 cases of renal tubular dysplasia, giving a calculated carrier animal frequency of 30.4% for the population.  The molecular description of the mutation and the availability of DNA tests allow breeders to identify carrier animals and eliminate the disease and the mutations from their stock via selective breeding.

 

References:

OMIA link: [1135-9913]

Sasaki S, Watanabe T, Ibi T, et al. (2021) Identification of deleterious recessive haplotypes and candidate deleterious recessive mutations in Japanese Black cattle. Sci Rep 11(1):6687.  [pm/33758295]

Ohba Y, Kitagawa H, Okura Y, et al. (2001) Clinical features of renal tubular dysplasia, a new hereditary disease in Japanese Black cattle. Veterinary Record 149(4):115-118.  [pm/11504203]

Hirano T, Hirotsune S, Sasaki S, et al. (2002) A new deletion mutation in bovine Claudin-16 (CL-16) deficiency and diagnosis Animal Genetics 33:118-122.  [pm/12047224]

Hirano T, Kobayashi N, Itoh T, et al. (2000) Null mutation of PCLN-1/Claudin-16 results in bovine chronic interstitial nephritis Genome Research 10(5):659-663. [pm/10810088]

Ohba Y, Kitagawa H, Kitoh K, et al. (2000) A deletion of the paracellin-1 gene is responsible for renal tubular dysplasia in cattle. Genomics 68(3):229-236.  [pm/10995564]

Kuwamura M, Kajimura K, Yamate J, et al. (1997) Renal disease in young Japanese black cattle. J Comp Path 116(1):101-106.  [pm/9076605]

 

Contributed by: Kim Cloutuer Rattelle and Albert Tannus, Class of 2028, Faculty of Veterinary Medicine, University of Montreal.  (Translation, DWS)