In other species: middle-African hedgehog , dog , domestic cat , horse

Categories: Renal / urinary system phene

Possibly relevant human trait(s) and/or gene(s) (MIM number): 248250 (trait)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2000

Species-specific name: Renal tubular dysplasia (RTD); Chronic interstitial nephritis with diffuse zonal fibrosis (CINF)

Species-specific symbol: RTD; CINF

History: The disorder was first described by Kuwamura et al. (1997)

Mapping: Two independent groups (Kobayashi et al., 2000; Ohba et al. 2000; Mammalian Genome 11:316-319) each used genome scans starting with more than 200 microsatellite markers to map the disorder to the central region of chromosome BTA1. Kobayashi et al. (2000) used a second set of 110 markers for fine-mapping, and then FISH-mapped a cosmid containing a relevant marker to BTA1q31-33. Ohba et al. (2000; Mammalian Genome 11:316-319) used homozygosity mapping to narrow the region to 4cM, and noted that this region is homologous to a region of human chromosome HSA3q that contains the gene paracellin-1 gene, mutations in which cause a related disorder in humans. Paracellin-1 thus became a comparative positional candidate gene.

Molecular basis: Building on the mapping results of Kobayashi et al. (2000) (see Mapping section above), Hirano et al. (2000) did some further fine mapping, and then constructed a cosmid library of the fine-mapped region of BTA1, and then used the best cosmid clone as a probe of kidney cDNA from normal and affected animals, identifying a single cDNA, which, when sequenced, turned out to be the bovine paracellin-1 gene, which they called Claudin-16, and which lacked exons 1-4 in affected animals. Independently, and building on the mapping results of Ohba et al. (2000; Mammalian Genome 11:316-319), Ohba et al. (2000; Genomics 68:229-236) did some further fine mapping and physical mapping of the region, and then identified and sequenced their comparative positional candidate gene, paracellin-1, revealing "a region of 37 kb including exons 1 to 4 of the bovine paracellin-1 gene was deleted in the affected animals". Thus both groups arrived at the same result at around the same time: the former paper was published in May 2000, and the latter in September 2000.

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Breed: Japanese Black, Japan (Cattle) (VBO_0004987).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: