Renal dysplasia in grey Alpine breed cattle unrelated to CLDN16 mutations

RENAL DYSPLASIA (RD) is a developmental disorder of the renal parenchyma characterized by anomalous differentiation of the nephrons and collecting ducts. In veterinary medicine, it has been described in several species, including cattle. In particular, in Japanese Black cattle, RD shows autosomal recessive inheritance, caused by CLDN16 mutations. This short communication deals with a case of RD in twin Grey Alpine heifers which is not related to mutations of the CLDN16 gene. RD should be considered when young animals show the following clinical findings: dullness, growth retardation, overgrowth of hooves and severe renal failure. Ultrasound can be strongly suggestive of RD, but only postmortem investigation can definitively confirm the disease. RD should be considered etiologically heterogeneous, as it is in human medicine. Eight-month-old twin Grey Alpine heifers were referred due to severe depression, poor appetite, growth retardation and overgrowth of hooves. Clinical biochemistry indicated the presence of renal failure. Ultrasonographic examination showed a severe disorganization of the renal parenchyma. Major finding was an increased echogenicity of both the renal cortex and the renal medulla. On gross postmortem examination the kidneys were hypotrophic, firm and pale, and had a roughened and granular surface. At the cut surface, dense cortical and medullar fibrosis, and fibrous wedges extending from the pelvis to the cortex were evident. At histopathology the kidneys showed diffuse and massive infiltration of immature mesenchymal tissue forming a net with evident parallel ridges, connected with transversal bridges, which gave a pseudo-lobular appearance to the renal tissue. The cortex was thin and presented primitive tubules lined by cuboidal epithelium on a thickened basal membrane, and immature glomeruli at different developmental stages. The medulla showed persistent mesenchyme and many primitive tubules lined by pseudostratified, columnar, epithelial cells. DNA of the affected animals, their dam as well as from a single unrelated animal, was screened for two different mutations of the CLDN16 gene responsible for inherited renal tubular dysplasia (RTD) in Japanese Black (Wagyu) cattle. The presence of a genomic deletion, such as that in Wagyu cattle, was excluded. Moreover, the re-sequencing of the PCR products revealed no polymorphisms affecting the coding sequence or consensus splice sites of CLDN16. This study showed a nephrologic syndrome phenotypically overlapping RD in Japanese Black cattle but which is not associated with mutations affecting the CLDN16 gene. Hopefully, this paper will alert bovine practitioners and breeders to the importance of reporting animals with the above-mentioned clinical findings to research or diagnostic centers for thorough evaluation.