Somatic inactivation of Pkd2 results in polycystic kidney disease

Guanqing Wu, Vivette D'Agati, Yiqiang Cai, Glen Markowitz, Jong Hoon Park, David M. Reynolds, Yoshiko Maeda, Thanh C. Le, Harry Hou, Raju Kucherlapati, Winfried Edelmann, Stefan Somlo

Research output: Contribution to journalArticle

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Abstract

Germline mutations in PKD2 cause autosomal dominant polycystic kidney disease. We have introduced a mutant exon 1 in tandem with the wild-type exon 1 at the mouse Pkd2 locus. This is an unstable allele that undergoes somatic inactivation by intragenic homologous recombination to produce a true null allele. Mice heterozygous and homozygous for this mutation, as well as Pkd+/- mice, develop polycystic kidney and liver lesions that are indistinguishable from the human phenotype. In all cases, renal cysts arise from renal tubular cells that lose the capacity to produce Pkd2 protein. Somatic loss of Pkd2 expression is both necessary and sufficient for renal cyst formation in ADPKD, suggesting that PKD2 occurs by a cellular recessive mechanism.

Original languageEnglish (US)
Pages (from-to)177-188
Number of pages12
JournalCell
Volume93
Issue number2
DOIs
StatePublished - Apr 17 1998

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Polycystic Kidney Diseases
Autosomal Dominant Polycystic Kidney
Exons
Kidney
Cysts
Alleles
Liver
Germ-Line Mutation
Homologous Recombination
Phenotype
Mutation
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Wu, G., D'Agati, V., Cai, Y., Markowitz, G., Park, J. H., Reynolds, D. M., ... Somlo, S. (1998). Somatic inactivation of Pkd2 results in polycystic kidney disease. Cell, 93(2), 177-188. https://doi.org/10.1016/S0092-8674(00)81570-6

Somatic inactivation of Pkd2 results in polycystic kidney disease. / Wu, Guanqing; D'Agati, Vivette; Cai, Yiqiang; Markowitz, Glen; Park, Jong Hoon; Reynolds, David M.; Maeda, Yoshiko; Le, Thanh C.; Hou, Harry; Kucherlapati, Raju; Edelmann, Winfried; Somlo, Stefan.

In: Cell, Vol. 93, No. 2, 17.04.1998, p. 177-188.

Research output: Contribution to journalArticle

Wu, G, D'Agati, V, Cai, Y, Markowitz, G, Park, JH, Reynolds, DM, Maeda, Y, Le, TC, Hou, H, Kucherlapati, R, Edelmann, W & Somlo, S 1998, 'Somatic inactivation of Pkd2 results in polycystic kidney disease', Cell, vol. 93, no. 2, pp. 177-188. https://doi.org/10.1016/S0092-8674(00)81570-6
Wu, Guanqing ; D'Agati, Vivette ; Cai, Yiqiang ; Markowitz, Glen ; Park, Jong Hoon ; Reynolds, David M. ; Maeda, Yoshiko ; Le, Thanh C. ; Hou, Harry ; Kucherlapati, Raju ; Edelmann, Winfried ; Somlo, Stefan. / Somatic inactivation of Pkd2 results in polycystic kidney disease. In: Cell. 1998 ; Vol. 93, No. 2. pp. 177-188.
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