Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel
CLC-K1 is a kidney-specific chloride channel that mediates transepithelial chloride transport in the thin ascending limb of Henle's loop (tAL) in the inner medulla 1 , 2 . Transport of NaCl in the tAL is thought to be a component of urinary concentration in a passive model of the countercurrent...
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| Veröffentlicht in: | Nature genetics 1999-01, Vol.21 (1), p.95-98 |
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| creator | Uchida, Shinichi Matsumura, Yoshihiro Kondo, Yoshiaki Miyazaki, Hiroaki Ko, Shigeru B.H Hayama, Atsushi Morimoto, Tetuji Liu, Wen Arisawa, Mikio Sasaki, Sei Marumo, Fumiaki |
| description | CLC-K1 is a kidney-specific chloride channel that mediates transepithelial chloride transport in the thin ascending limb of Henle's loop (tAL) in the inner medulla
1
,
2
. Transport of NaCl in the tAL is thought to be a component of urinary concentration in a passive model of the countercurrent multiplication system
3
,
4
,
5
, but there has been no direct evidence that CLC-K1 is involved in urine concentration. To analyse the physiological function of CLC-K1
in vivo
, we generated mice lacking CLC-K1 by targeted gene disruption.
Clcnk1
–/–
mice were physically normal appearance, but produced approximately five times more urine than
Clcnk1
+/–
and
Clcnk1
+/+
mice. After 24 hours of water deprivation,
Clcnk1
–/–
mice were severely dehydrated and lethargic, with a decrease of approximately 27% in body weight. Intraperitoneal injection of the V2 agonist 1-deamino-8-D-arginine vasopressin (dDAVP) induced a threefold increase in urine osmolarity in
Clcnk1
+/–
and
Clcnk1
+/+
mice, whereas only a minimal increase was seen in
Clcnk1
–/–
mice, indicating nephrogenic diabetes insipidus. After
in vitro
perfusion of the tAL, the lumen-to-bath chloride gradient did not produce a diffusion potential in
Clcnk1
–/–
mice in contrast to
Clcnk1
+/+
and
Clcnk1
+/–
mice. These results establish that CLC-K1 has a role in urine concentration, and that the countercurrent system in the inner medulla is involved in the generation and maintenance of hypertonic medullary interstitium. |
| doi_str_mv | 10.1038/5036 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_69550922</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>17218748</sourcerecordid><originalsourceid>FETCH-LOGICAL-c384t-2380d1755179d37937df9a98258ba7b5d2b2e70b9a78d9f2261c76da327e2dcf3</originalsourceid><addsrcrecordid>eNqFkMtKxDAUhoMo3h9B7ELdVXNpbksZvOGALnRd0uR0JtpJa9IKvr0dZ3DAjavzc87Hd-BH6IjgS4KZuuKYiS20T3ghciKJ2h4zFiQvxv0eOkjpDWNSFFjtol2tiZBa7aPnp0-IfRagm8d2BsHbzHlTQQ8p8yH5zrthmbKFt5A1xr77MMv6OWST6SR_JJmdN230DsZgQoDmCO3UpklwvJ6H6PX25mVyn0-f7h4m19PcMlX0OWUKOyI5J1I7JjWTrtZGK8pVZWTFHa0oSFxpI5XTNaWCWCmcYVQCdbZmh-hi5e1i-zFA6suFTxaaxgRoh1QKzTnWlP4LEkmJkoUawbMVaGObUoS67KJfmPhVElwuGy6XDY_Yydo3VAtwv9C60o2mM8mapo4mWJ82LiEo-8HOV1gaL2EGsXxrhxjGyv6-O11xwfRDhF9PmGGidak5-wboc5cQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17218748</pqid></control><display><type>article</type><title>Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel</title><source>MEDLINE</source><source>SpringerNature Journals</source><source>Nature Journals Online</source><creator>Uchida, Shinichi ; Matsumura, Yoshihiro ; Kondo, Yoshiaki ; Miyazaki, Hiroaki ; Ko, Shigeru B.H ; Hayama, Atsushi ; Morimoto, Tetuji ; Liu, Wen ; Arisawa, Mikio ; Sasaki, Sei ; Marumo, Fumiaki</creator><creatorcontrib>Uchida, Shinichi ; Matsumura, Yoshihiro ; Kondo, Yoshiaki ; Miyazaki, Hiroaki ; Ko, Shigeru B.H ; Hayama, Atsushi ; Morimoto, Tetuji ; Liu, Wen ; Arisawa, Mikio ; Sasaki, Sei ; Marumo, Fumiaki</creatorcontrib><description>CLC-K1 is a kidney-specific chloride channel that mediates transepithelial chloride transport in the thin ascending limb of Henle's loop (tAL) in the inner medulla
1
,
2
. Transport of NaCl in the tAL is thought to be a component of urinary concentration in a passive model of the countercurrent multiplication system
3
,
4
,
5
, but there has been no direct evidence that CLC-K1 is involved in urine concentration. To analyse the physiological function of CLC-K1
in vivo
, we generated mice lacking CLC-K1 by targeted gene disruption.
Clcnk1
–/–
mice were physically normal appearance, but produced approximately five times more urine than
Clcnk1
+/–
and
Clcnk1
+/+
mice. After 24 hours of water deprivation,
Clcnk1
–/–
mice were severely dehydrated and lethargic, with a decrease of approximately 27% in body weight. Intraperitoneal injection of the V2 agonist 1-deamino-8-D-arginine vasopressin (dDAVP) induced a threefold increase in urine osmolarity in
Clcnk1
+/–
and
Clcnk1
+/+
mice, whereas only a minimal increase was seen in
Clcnk1
–/–
mice, indicating nephrogenic diabetes insipidus. After
in vitro
perfusion of the tAL, the lumen-to-bath chloride gradient did not produce a diffusion potential in
Clcnk1
–/–
mice in contrast to
Clcnk1
+/+
and
Clcnk1
+/–
mice. These results establish that CLC-K1 has a role in urine concentration, and that the countercurrent system in the inner medulla is involved in the generation and maintenance of hypertonic medullary interstitium.</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/5036</identifier><identifier>PMID: 9916798</identifier><identifier>CODEN: NGENEC</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Agriculture ; Animal Genetics and Genomics ; Animals ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Chloride Channels - genetics ; Chloride Channels - physiology ; Classical genetics, quantitative genetics, hybrids ; Diabetes Insipidus, Nephrogenic - blood ; Diabetes Insipidus, Nephrogenic - etiology ; Diabetes Insipidus, Nephrogenic - urine ; Disease Models, Animal ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Function ; Genetics of eukaryotes. Biological and molecular evolution ; Human Genetics ; letter ; Loop of Henle - physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Vertebrata</subject><ispartof>Nature genetics, 1999-01, Vol.21 (1), p.95-98</ispartof><rights>Nature America Inc. 1999</rights><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-2380d1755179d37937df9a98258ba7b5d2b2e70b9a78d9f2261c76da327e2dcf3</citedby><cites>FETCH-LOGICAL-c384t-2380d1755179d37937df9a98258ba7b5d2b2e70b9a78d9f2261c76da327e2dcf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/5036$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/5036$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,2727,4024,27923,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1662398$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9916798$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Uchida, Shinichi</creatorcontrib><creatorcontrib>Matsumura, Yoshihiro</creatorcontrib><creatorcontrib>Kondo, Yoshiaki</creatorcontrib><creatorcontrib>Miyazaki, Hiroaki</creatorcontrib><creatorcontrib>Ko, Shigeru B.H</creatorcontrib><creatorcontrib>Hayama, Atsushi</creatorcontrib><creatorcontrib>Morimoto, Tetuji</creatorcontrib><creatorcontrib>Liu, Wen</creatorcontrib><creatorcontrib>Arisawa, Mikio</creatorcontrib><creatorcontrib>Sasaki, Sei</creatorcontrib><creatorcontrib>Marumo, Fumiaki</creatorcontrib><title>Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>CLC-K1 is a kidney-specific chloride channel that mediates transepithelial chloride transport in the thin ascending limb of Henle's loop (tAL) in the inner medulla
1
,
2
. Transport of NaCl in the tAL is thought to be a component of urinary concentration in a passive model of the countercurrent multiplication system
3
,
4
,
5
, but there has been no direct evidence that CLC-K1 is involved in urine concentration. To analyse the physiological function of CLC-K1
in vivo
, we generated mice lacking CLC-K1 by targeted gene disruption.
Clcnk1
–/–
mice were physically normal appearance, but produced approximately five times more urine than
Clcnk1
+/–
and
Clcnk1
+/+
mice. After 24 hours of water deprivation,
Clcnk1
–/–
mice were severely dehydrated and lethargic, with a decrease of approximately 27% in body weight. Intraperitoneal injection of the V2 agonist 1-deamino-8-D-arginine vasopressin (dDAVP) induced a threefold increase in urine osmolarity in
Clcnk1
+/–
and
Clcnk1
+/+
mice, whereas only a minimal increase was seen in
Clcnk1
–/–
mice, indicating nephrogenic diabetes insipidus. After
in vitro
perfusion of the tAL, the lumen-to-bath chloride gradient did not produce a diffusion potential in
Clcnk1
–/–
mice in contrast to
Clcnk1
+/+
and
Clcnk1
+/–
mice. These results establish that CLC-K1 has a role in urine concentration, and that the countercurrent system in the inner medulla is involved in the generation and maintenance of hypertonic medullary interstitium.</description><subject>Agriculture</subject><subject>Animal Genetics and Genomics</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Chloride Channels - genetics</subject><subject>Chloride Channels - physiology</subject><subject>Classical genetics, quantitative genetics, hybrids</subject><subject>Diabetes Insipidus, Nephrogenic - blood</subject><subject>Diabetes Insipidus, Nephrogenic - etiology</subject><subject>Diabetes Insipidus, Nephrogenic - urine</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Function</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Human Genetics</subject><subject>letter</subject><subject>Loop of Henle - physiopathology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Vertebrata</subject><issn>1061-4036</issn><issn>1546-1718</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtKxDAUhoMo3h9B7ELdVXNpbksZvOGALnRd0uR0JtpJa9IKvr0dZ3DAjavzc87Hd-BH6IjgS4KZuuKYiS20T3ghciKJ2h4zFiQvxv0eOkjpDWNSFFjtol2tiZBa7aPnp0-IfRagm8d2BsHbzHlTQQ8p8yH5zrthmbKFt5A1xr77MMv6OWST6SR_JJmdN230DsZgQoDmCO3UpklwvJ6H6PX25mVyn0-f7h4m19PcMlX0OWUKOyI5J1I7JjWTrtZGK8pVZWTFHa0oSFxpI5XTNaWCWCmcYVQCdbZmh-hi5e1i-zFA6suFTxaaxgRoh1QKzTnWlP4LEkmJkoUawbMVaGObUoS67KJfmPhVElwuGy6XDY_Yydo3VAtwv9C60o2mM8mapo4mWJ82LiEo-8HOV1gaL2EGsXxrhxjGyv6-O11xwfRDhF9PmGGidak5-wboc5cQ</recordid><startdate>199901</startdate><enddate>199901</enddate><creator>Uchida, Shinichi</creator><creator>Matsumura, Yoshihiro</creator><creator>Kondo, Yoshiaki</creator><creator>Miyazaki, Hiroaki</creator><creator>Ko, Shigeru B.H</creator><creator>Hayama, Atsushi</creator><creator>Morimoto, Tetuji</creator><creator>Liu, Wen</creator><creator>Arisawa, Mikio</creator><creator>Sasaki, Sei</creator><creator>Marumo, Fumiaki</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>IQODW</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>199901</creationdate><title>Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel</title><author>Uchida, Shinichi ; Matsumura, Yoshihiro ; Kondo, Yoshiaki ; Miyazaki, Hiroaki ; Ko, Shigeru B.H ; Hayama, Atsushi ; Morimoto, Tetuji ; Liu, Wen ; Arisawa, Mikio ; Sasaki, Sei ; Marumo, Fumiaki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-2380d1755179d37937df9a98258ba7b5d2b2e70b9a78d9f2261c76da327e2dcf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Agriculture</topic><topic>Animal Genetics and Genomics</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Chloride Channels - genetics</topic><topic>Chloride Channels - physiology</topic><topic>Classical genetics, quantitative genetics, hybrids</topic><topic>Diabetes Insipidus, Nephrogenic - blood</topic><topic>Diabetes Insipidus, Nephrogenic - etiology</topic><topic>Diabetes Insipidus, Nephrogenic - urine</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Function</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Human Genetics</topic><topic>letter</topic><topic>Loop of Henle - physiopathology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Vertebrata</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Uchida, Shinichi</creatorcontrib><creatorcontrib>Matsumura, Yoshihiro</creatorcontrib><creatorcontrib>Kondo, Yoshiaki</creatorcontrib><creatorcontrib>Miyazaki, Hiroaki</creatorcontrib><creatorcontrib>Ko, Shigeru B.H</creatorcontrib><creatorcontrib>Hayama, Atsushi</creatorcontrib><creatorcontrib>Morimoto, Tetuji</creatorcontrib><creatorcontrib>Liu, Wen</creatorcontrib><creatorcontrib>Arisawa, Mikio</creatorcontrib><creatorcontrib>Sasaki, Sei</creatorcontrib><creatorcontrib>Marumo, Fumiaki</creatorcontrib><collection>Pascal-Francis</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>Nature genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Uchida, Shinichi</au><au>Matsumura, Yoshihiro</au><au>Kondo, Yoshiaki</au><au>Miyazaki, Hiroaki</au><au>Ko, Shigeru B.H</au><au>Hayama, Atsushi</au><au>Morimoto, Tetuji</au><au>Liu, Wen</au><au>Arisawa, Mikio</au><au>Sasaki, Sei</au><au>Marumo, Fumiaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><addtitle>Nat Genet</addtitle><date>1999-01</date><risdate>1999</risdate><volume>21</volume><issue>1</issue><spage>95</spage><epage>98</epage><pages>95-98</pages><issn>1061-4036</issn><eissn>1546-1718</eissn><coden>NGENEC</coden><abstract>CLC-K1 is a kidney-specific chloride channel that mediates transepithelial chloride transport in the thin ascending limb of Henle's loop (tAL) in the inner medulla
1
,
2
. Transport of NaCl in the tAL is thought to be a component of urinary concentration in a passive model of the countercurrent multiplication system
3
,
4
,
5
, but there has been no direct evidence that CLC-K1 is involved in urine concentration. To analyse the physiological function of CLC-K1
in vivo
, we generated mice lacking CLC-K1 by targeted gene disruption.
Clcnk1
–/–
mice were physically normal appearance, but produced approximately five times more urine than
Clcnk1
+/–
and
Clcnk1
+/+
mice. After 24 hours of water deprivation,
Clcnk1
–/–
mice were severely dehydrated and lethargic, with a decrease of approximately 27% in body weight. Intraperitoneal injection of the V2 agonist 1-deamino-8-D-arginine vasopressin (dDAVP) induced a threefold increase in urine osmolarity in
Clcnk1
+/–
and
Clcnk1
+/+
mice, whereas only a minimal increase was seen in
Clcnk1
–/–
mice, indicating nephrogenic diabetes insipidus. After
in vitro
perfusion of the tAL, the lumen-to-bath chloride gradient did not produce a diffusion potential in
Clcnk1
–/–
mice in contrast to
Clcnk1
+/+
and
Clcnk1
+/–
mice. These results establish that CLC-K1 has a role in urine concentration, and that the countercurrent system in the inner medulla is involved in the generation and maintenance of hypertonic medullary interstitium.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>9916798</pmid><doi>10.1038/5036</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1061-4036 |
| ispartof | Nature genetics, 1999-01, Vol.21 (1), p.95-98 |
| issn | 1061-4036 1546-1718 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_69550922 |
| source | MEDLINE; SpringerNature Journals; Nature Journals Online |
| subjects | Agriculture Animal Genetics and Genomics Animals Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Chloride Channels - genetics Chloride Channels - physiology Classical genetics, quantitative genetics, hybrids Diabetes Insipidus, Nephrogenic - blood Diabetes Insipidus, Nephrogenic - etiology Diabetes Insipidus, Nephrogenic - urine Disease Models, Animal Female Fundamental and applied biological sciences. Psychology Gene Function Genetics of eukaryotes. Biological and molecular evolution Human Genetics letter Loop of Henle - physiopathology Male Mice Mice, Inbred C57BL Mice, Knockout Vertebrata |
| title | Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel |
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