Somatic Inactivation of Pkd2 Results in Polycystic Kidney Disease
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...
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| Veröffentlicht in: | Cell 1998-04, Vol.93 (2), p.177-188 |
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| container_title | Cell |
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| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1016/S0092-8674(00)81570-6 |
| format | Article |
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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.</description><identifier>ISSN: 0092-8674</identifier><identifier>EISSN: 1097-4172</identifier><identifier>DOI: 10.1016/S0092-8674(00)81570-6</identifier><identifier>PMID: 9568711</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Alleles ; Animals ; Clone Cells ; Crosses, Genetic ; DNA - analysis ; Exons - genetics ; Genotype ; Kidney - chemistry ; Kidney - pathology ; Liver - pathology ; Loss of Heterozygosity ; Membrane Proteins - analysis ; Membrane Proteins - genetics ; Membrane Proteins - physiology ; Mice ; Mice, Knockout ; Mutation - physiology ; Polycystic Kidney, Autosomal Dominant - genetics ; Polycystic Kidney, Autosomal Dominant - pathology ; Recombination, Genetic ; Restriction Mapping ; RNA, Messenger - analysis ; Stem Cells ; TRPP Cation Channels</subject><ispartof>Cell, 1998-04, Vol.93 (2), p.177-188</ispartof><rights>1998 Cell Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-cc4a49df0fff00eb556823a125ec72922ba68380b2fb26dbc4c234ccf63347603</citedby><cites>FETCH-LOGICAL-c504t-cc4a49df0fff00eb556823a125ec72922ba68380b2fb26dbc4c234ccf63347603</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0092867400815706$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9568711$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Guanqing</creatorcontrib><creatorcontrib>D'Agati, Vivette</creatorcontrib><creatorcontrib>Cai, Yiqiang</creatorcontrib><creatorcontrib>Markowitz, Glen</creatorcontrib><creatorcontrib>Park, Jong Hoon</creatorcontrib><creatorcontrib>Reynolds, David M</creatorcontrib><creatorcontrib>Maeda, Yoshiko</creatorcontrib><creatorcontrib>Le, Thanh C</creatorcontrib><creatorcontrib>Hou, Harry</creatorcontrib><creatorcontrib>Kucherlapati, Raju</creatorcontrib><creatorcontrib>Edelmann, Winfried</creatorcontrib><creatorcontrib>Somlo, Stefan</creatorcontrib><title>Somatic Inactivation of Pkd2 Results in Polycystic Kidney Disease</title><title>Cell</title><addtitle>Cell</addtitle><description>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.</description><subject>Alleles</subject><subject>Animals</subject><subject>Clone Cells</subject><subject>Crosses, Genetic</subject><subject>DNA - analysis</subject><subject>Exons - genetics</subject><subject>Genotype</subject><subject>Kidney - chemistry</subject><subject>Kidney - pathology</subject><subject>Liver - pathology</subject><subject>Loss of Heterozygosity</subject><subject>Membrane Proteins - analysis</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - physiology</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mutation - physiology</subject><subject>Polycystic Kidney, Autosomal Dominant - genetics</subject><subject>Polycystic Kidney, Autosomal Dominant - pathology</subject><subject>Recombination, Genetic</subject><subject>Restriction Mapping</subject><subject>RNA, Messenger - analysis</subject><subject>Stem Cells</subject><subject>TRPP Cation Channels</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1Lw0AQhhdRaq3-hEJOoofo7GY_kpOU-lUsWKyel81mFlbTpGbTQv-96Qe9epqBeWbe4SFkSOGOApX3c4CMxalU_AbgNqVCQSxPSJ9CpmJOFTsl_SNyTi5C-AaAVAjRI71MyFRR2iejeb0wrbfRpDK29euur6uodtHsp2DRB4ZV2YbIV9GsLjd2E7bomy8q3ESPPqAJeEnOnCkDXh3qgHw9P32OX-Pp-8tkPJrGVgBvY2u54VnhwDkHgLnoPmCJoUygVSxjLDcyTVLImcuZLHLLLUu4tU4mCVcSkgG53t9dNvXvCkOrFz5YLEtTYb0KWmUpkyDlvyCVHLhiaQeKPWibOoQGnV42fmGajaagt471zrHeCtQAeudYbwOGh4BVvsDiuHWQ2s0f9nPsdKw9NjpYj5XFwjdoW13U_p-EP0WbioI</recordid><startdate>19980417</startdate><enddate>19980417</enddate><creator>Wu, Guanqing</creator><creator>D'Agati, Vivette</creator><creator>Cai, Yiqiang</creator><creator>Markowitz, Glen</creator><creator>Park, Jong Hoon</creator><creator>Reynolds, David M</creator><creator>Maeda, Yoshiko</creator><creator>Le, Thanh C</creator><creator>Hou, Harry</creator><creator>Kucherlapati, Raju</creator><creator>Edelmann, Winfried</creator><creator>Somlo, Stefan</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>19980417</creationdate><title>Somatic Inactivation of Pkd2 Results in Polycystic Kidney Disease</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-cc4a49df0fff00eb556823a125ec72922ba68380b2fb26dbc4c234ccf63347603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Alleles</topic><topic>Animals</topic><topic>Clone Cells</topic><topic>Crosses, Genetic</topic><topic>DNA - analysis</topic><topic>Exons - genetics</topic><topic>Genotype</topic><topic>Kidney - chemistry</topic><topic>Kidney - pathology</topic><topic>Liver - pathology</topic><topic>Loss of Heterozygosity</topic><topic>Membrane Proteins - analysis</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - physiology</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mutation - physiology</topic><topic>Polycystic Kidney, Autosomal Dominant - genetics</topic><topic>Polycystic Kidney, Autosomal Dominant - pathology</topic><topic>Recombination, Genetic</topic><topic>Restriction Mapping</topic><topic>RNA, Messenger - analysis</topic><topic>Stem Cells</topic><topic>TRPP Cation Channels</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Guanqing</creatorcontrib><creatorcontrib>D'Agati, Vivette</creatorcontrib><creatorcontrib>Cai, Yiqiang</creatorcontrib><creatorcontrib>Markowitz, Glen</creatorcontrib><creatorcontrib>Park, Jong Hoon</creatorcontrib><creatorcontrib>Reynolds, David M</creatorcontrib><creatorcontrib>Maeda, Yoshiko</creatorcontrib><creatorcontrib>Le, Thanh C</creatorcontrib><creatorcontrib>Hou, Harry</creatorcontrib><creatorcontrib>Kucherlapati, Raju</creatorcontrib><creatorcontrib>Edelmann, Winfried</creatorcontrib><creatorcontrib>Somlo, Stefan</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Guanqing</au><au>D'Agati, Vivette</au><au>Cai, Yiqiang</au><au>Markowitz, Glen</au><au>Park, Jong Hoon</au><au>Reynolds, David M</au><au>Maeda, Yoshiko</au><au>Le, Thanh C</au><au>Hou, Harry</au><au>Kucherlapati, Raju</au><au>Edelmann, Winfried</au><au>Somlo, Stefan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Somatic Inactivation of Pkd2 Results in Polycystic Kidney Disease</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>1998-04-17</date><risdate>1998</risdate><volume>93</volume><issue>2</issue><spage>177</spage><epage>188</epage><pages>177-188</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>9568711</pmid><doi>10.1016/S0092-8674(00)81570-6</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Alleles Animals Clone Cells Crosses, Genetic DNA - analysis Exons - genetics Genotype Kidney - chemistry Kidney - pathology Liver - pathology Loss of Heterozygosity Membrane Proteins - analysis Membrane Proteins - genetics Membrane Proteins - physiology Mice Mice, Knockout Mutation - physiology Polycystic Kidney, Autosomal Dominant - genetics Polycystic Kidney, Autosomal Dominant - pathology Recombination, Genetic Restriction Mapping RNA, Messenger - analysis Stem Cells TRPP Cation Channels |
| title | Somatic Inactivation of Pkd2 Results in Polycystic Kidney Disease |
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