Canine PKD1 is a single-copy gene: genomic organization and comparative analysis.
Most cases of autosomal dominant polycystic kidney disease are caused by mutations in the gene PKD1, encoding polycystin-1. To gain insight into the role of polycystin-1 in tubulogenesis and cystogenesis using the well-characterized canine kidney epithelial cell line MDCK, we have now cloned and characterized the exon/intron structure of the canine gene PKD1. FISH analysis showed that the dog genome lacks the multiple PKD1 homologs present in human. Intron 21 of dog PKD1 lacked the polypyrimidine tract characteristic of the human gene, whereas pyrimidine-rich elements were identified in canine intron 30. Canine polycystin-1 showed a higher degree of homology with the human counterpart and lower homology with mouse and rat. A striking degree of conservation (97% identity) was determined for the leucine-rich repeat domain between dog and human. Also, the homology analysis indicated that 4 of 16 Ig-like repeats (IgIII, IgVII, IgX, and IgXV) are likely to be functionally significant. This is particularly important in light of our recent findings demonstrating that Iglike domains form strong homophilic interactions and can mediate cell-cell adhesion. These data enable detailed analysis of the role of polycystin-1 in cystogenesis and tubulogenesis using the canine MDCK cell line.
Dackowski
William R
WR
Genzyme Corporation, 5 Mountain Road, Framingham, Massachusetts, 01701-9322, USA.
Luderer
Hilary F
HF
Manavalan
Partha
P
Bukanov
Nikolay O
NO
Russo
Ryan J
RJ
Roberts
Bruce L
BL
Klinger
Katherine W
KW
Ibraghimov-Beskrovnaya
Oxana
O
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D004285:Dogs / Q000235:genetics*; D005091:Exons; D018628:Gene Dosage; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D050396:TRPP Cation Channels
D011506:Proteins; D050396:TRPP Cation Channels