Kidney Week

Abstract: TH-PO582

Anks3 and Anks6 Expression Pattern and Co-Localization in the Kidney Is Tightly Regulated during Development and Disturbed by the Anks6pR823W Mutation in Rats with ADPKD

Session Information

• Cystic Kidney Diseases - I
  November 02, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Genetic Diseases of the Kidney

• 801 Cystic Kidney Diseases

Authors

• Clark, Euan, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

Euan Clark,

• Papagiannarou, Stamatia Matina, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

Stamatia Matina Papagiannarou,

• Bowie, James, University of California, Los Angeles, Los Angeles, California, United States

James Bowie,

• Hoffmann, Sigrid C., Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

Sigrid C. Hoffmann,

Background

Autosomal dominant polycystic kidney disease (ADPKD) in rats is caused by a missense mutation in Anks6 (Anks6^pR823W). The Anks6^pR823W mutation disrupts the interaction between the SAM domains of Anks6 and Anks3, a novel protein. The function of this interaction is unknown. Co-localization of Anks6 and Anks3 is a precondition that interaction can occur. Thus, this study aimed to analyze the spatial and developmental renal expression pattern of Anks6 and Anks3 in WT and Anks6^pR823W cy/cy rats.

Methods

Anks3 and Anks6 expression were studied during renal development (0- and 10-days of life) and in the mature kidney at the age of 4 weeks in normal wild type (WT) and homozygous Anks6^pR823W cy/cy rats by in situ hybridization, immunohistochemistry and confocal microscopy.

Results

In kidneys of 0d -10d old WT rats both, Anks6 and Anks3, were expressed only in the cortex, not in the medulla and do not co-localize. In contrast, in the mature WT kidney both, Anks3 and Anks6, are strikingly expressed in the medullary collecting ducts and co-localizes with aquaporin 2 (Aqp2). In the renal cortex they co-localizes in distal tubules, however, only Anks6 but not Anks3 expression was noted in the S3 segment of the proximal tubule; the tubular segment in which cysts originate in Anks6^pR823W cy/cy rats. Unlike WT kidneys, Anks6^pR823W cy/cy rats already show during kidney development a strong expression and co-localization of Anks6 and Anks3 in the medullary collecting ducts and the cortical tubules. The Aqp2 expression is significantly less in both, 0d -10d old and mature kidneys, of cy/cy rats when compared with WT rats indicating a reduced water retention.

Conclusion

A developmental regulated spatial expression pattern of Anks6 and Anks3 exist in the WT kidney, which is disturbed in Anks6^pR823W cy/cy rats. Since we have previously shown that Anks3 knockout in rats decreases urine production and increases Aqp2 expression, data suggests that Anks3 is overactive in Anks6^pR823W and suppresses Aqp2 expression. In WT kidneys, Anks6 and Anks3 interaction via their SAM domain might block this Anks3 effect. Further studies are required to relate these findings to the cystogenesis. This study was supported by the grant of the NIH (5RO1DK100482) to JB and SH

Funding

• NIDDK Support