Pathogenesis of Renal Injury in the Megabladder Mouse: A Genetic Model of Congenital Obstructive Nephropathy
Congenital obstructive nephropathy (CON) is the most common cause of chronic renal failure in children often leading to end-stage renal disease. The megabladder ( mgb ) mouse exhibits signs of urinary tract obstruction in utero resulting in the development of hydroureteronephrosis and progressive re...
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| Veröffentlicht in: | Pediatric research 2010-12, Vol.68 (6), p.500-507 |
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| creator | Ingraham, Susan E Saha, Monalee Carpenter, Ashley R Robinson, Melissa Ismail, Ihab Singh, Sunita Hains, David Robinson, Michael L Hirselj, Daniel A Koff, Stephen A Bates, Carlton M McHugh, Kirk M |
| description | Congenital obstructive nephropathy (CON) is the most common cause of chronic renal failure in children often leading to end-stage renal disease. The megabladder (
mgb
) mouse exhibits signs of urinary tract obstruction
in utero
resulting in the development of hydroureteronephrosis and progressive renal failure after birth. This study examined the development of progressive renal injury in homozygous
mgb
mice (
mgb−/−
). Renal ultrasound was used to stratify the disease state of
mgb−
/
−
mice, whereas surgical rescue was performed using vesicostomy. The progression of renal injury was characterized using a series of pathogenic markers including alpha smooth muscle isoactin (α-SMA), TGF-β1, connective tissue growth factor (CTGF), E-cadherin, F4/80, Wilm's tumor (WT)-1, and paired box gene (Pax) 2. This analysis indicated that
mgb−
/
−
mice are born with pathologic changes in kidney development that progressively worsen in direct correlation with the severity of hydronephrosis. The initiation and pattern of fibrotic development observed in
mgb−
/
−
kidneys appeared distinctive from previous animal models of obstruction. These observations suggest that the
mgb
mouse represents a unique small animal model for the study of CON. |
| doi_str_mv | 10.1203/PDR.0b013e3181f82f15 |
| format | Article |
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mgb
) mouse exhibits signs of urinary tract obstruction
in utero
resulting in the development of hydroureteronephrosis and progressive renal failure after birth. This study examined the development of progressive renal injury in homozygous
mgb
mice (
mgb−/−
). Renal ultrasound was used to stratify the disease state of
mgb−
/
−
mice, whereas surgical rescue was performed using vesicostomy. The progression of renal injury was characterized using a series of pathogenic markers including alpha smooth muscle isoactin (α-SMA), TGF-β1, connective tissue growth factor (CTGF), E-cadherin, F4/80, Wilm's tumor (WT)-1, and paired box gene (Pax) 2. This analysis indicated that
mgb−
/
−
mice are born with pathologic changes in kidney development that progressively worsen in direct correlation with the severity of hydronephrosis. The initiation and pattern of fibrotic development observed in
mgb−
/
−
kidneys appeared distinctive from previous animal models of obstruction. These observations suggest that the
mgb
mouse represents a unique small animal model for the study of CON.</description><identifier>ISSN: 0031-3998</identifier><identifier>EISSN: 1530-0447</identifier><identifier>DOI: 10.1203/PDR.0b013e3181f82f15</identifier><identifier>PMID: 20736884</identifier><identifier>CODEN: PEREBL</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Animals ; basic-science-investigation ; Biological and medical sciences ; Child ; Cystostomy ; Disease Models, Animal ; Disease Progression ; Fibrosis ; General aspects ; Humans ; Hydronephrosis - complications ; Hydronephrosis - congenital ; Hydronephrosis - pathology ; Hydronephrosis - surgery ; Kidney - diagnostic imaging ; Kidney - injuries ; Kidney - pathology ; Kidney Failure, Chronic - congenital ; Kidney Failure, Chronic - etiology ; Kidney Failure, Chronic - pathology ; Kidney Failure, Chronic - surgery ; Kidneys ; Male ; Medical sciences ; Medicine ; Medicine & Public Health ; Mice ; Mice, Knockout ; Mice, Mutant Strains ; Nephritis, Interstitial - complications ; Nephritis, Interstitial - congenital ; Nephritis, Interstitial - pathology ; Nephritis, Interstitial - surgery ; Nephrology. Urinary tract diseases ; Pediatric Surgery ; Pediatrics ; Ultrasonography ; Urinary system involvement in other diseases. Miscellaneous ; Urinary tract. Prostate gland</subject><ispartof>Pediatric research, 2010-12, Vol.68 (6), p.500-507</ispartof><rights>International Pediatrics Research Foundation, Inc. 2010</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-4104ce9af981325f5af4c745b8b19faee634acbc614c1f4942037d930efdf1dd3</citedby><cites>FETCH-LOGICAL-c483t-4104ce9af981325f5af4c745b8b19faee634acbc614c1f4942037d930efdf1dd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,886,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23530595$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20736884$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ingraham, Susan E</creatorcontrib><creatorcontrib>Saha, Monalee</creatorcontrib><creatorcontrib>Carpenter, Ashley R</creatorcontrib><creatorcontrib>Robinson, Melissa</creatorcontrib><creatorcontrib>Ismail, Ihab</creatorcontrib><creatorcontrib>Singh, Sunita</creatorcontrib><creatorcontrib>Hains, David</creatorcontrib><creatorcontrib>Robinson, Michael L</creatorcontrib><creatorcontrib>Hirselj, Daniel A</creatorcontrib><creatorcontrib>Koff, Stephen A</creatorcontrib><creatorcontrib>Bates, Carlton M</creatorcontrib><creatorcontrib>McHugh, Kirk M</creatorcontrib><title>Pathogenesis of Renal Injury in the Megabladder Mouse: A Genetic Model of Congenital Obstructive Nephropathy</title><title>Pediatric research</title><addtitle>Pediatr Res</addtitle><addtitle>Pediatr Res</addtitle><description>Congenital obstructive nephropathy (CON) is the most common cause of chronic renal failure in children often leading to end-stage renal disease. The megabladder (
mgb
) mouse exhibits signs of urinary tract obstruction
in utero
resulting in the development of hydroureteronephrosis and progressive renal failure after birth. This study examined the development of progressive renal injury in homozygous
mgb
mice (
mgb−/−
). Renal ultrasound was used to stratify the disease state of
mgb−
/
−
mice, whereas surgical rescue was performed using vesicostomy. The progression of renal injury was characterized using a series of pathogenic markers including alpha smooth muscle isoactin (α-SMA), TGF-β1, connective tissue growth factor (CTGF), E-cadherin, F4/80, Wilm's tumor (WT)-1, and paired box gene (Pax) 2. This analysis indicated that
mgb−
/
−
mice are born with pathologic changes in kidney development that progressively worsen in direct correlation with the severity of hydronephrosis. The initiation and pattern of fibrotic development observed in
mgb−
/
−
kidneys appeared distinctive from previous animal models of obstruction. These observations suggest that the
mgb
mouse represents a unique small animal model for the study of CON.</description><subject>Animals</subject><subject>basic-science-investigation</subject><subject>Biological and medical sciences</subject><subject>Child</subject><subject>Cystostomy</subject><subject>Disease Models, Animal</subject><subject>Disease Progression</subject><subject>Fibrosis</subject><subject>General aspects</subject><subject>Humans</subject><subject>Hydronephrosis - complications</subject><subject>Hydronephrosis - congenital</subject><subject>Hydronephrosis - pathology</subject><subject>Hydronephrosis - surgery</subject><subject>Kidney - diagnostic imaging</subject><subject>Kidney - injuries</subject><subject>Kidney - pathology</subject><subject>Kidney Failure, Chronic - congenital</subject><subject>Kidney Failure, Chronic - etiology</subject><subject>Kidney Failure, Chronic - pathology</subject><subject>Kidney Failure, Chronic - surgery</subject><subject>Kidneys</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mice, Mutant Strains</subject><subject>Nephritis, Interstitial - complications</subject><subject>Nephritis, Interstitial - congenital</subject><subject>Nephritis, Interstitial - pathology</subject><subject>Nephritis, Interstitial - surgery</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Pediatric Surgery</subject><subject>Pediatrics</subject><subject>Ultrasonography</subject><subject>Urinary system involvement in other diseases. Miscellaneous</subject><subject>Urinary tract. Prostate gland</subject><issn>0031-3998</issn><issn>1530-0447</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtvEzEUhS0EoqHwDxDyBrGa4jv2ZGwWSFWAUqmlVQVry-O5Thw549SeqZR_j6OE8liwsuT7nXMfh5DXwM6gZvz97ae7M9Yx4MhBgpO1g-YJmUHDWcWEaJ-SGWMcKq6UPCEvcl4zBqKR4jk5qVnL51KKGQm3ZlzFJQ6YfabR0TscTKCXw3pKO-oHOq6QXuPSdMH0PSZ6HaeMH-g5vSia0dvy0WPYKxdxKD5-LPKbLo9psqN_QPoNt6sUt6XN7iV55kzI-Or4npIfXz5_X3ytrm4uLhfnV5UVko-VACYsKuOUBF43rjFO2FY0nexAOYM458LYzs5BWHBCiXKOtlecoesd9D0_JR8Pvtup22BvcRiTCXqb_MaknY7G678rg1_pZXzQHGpQAMXg3dEgxfsJ86g3PlsMwQxY9tdSllMyMW8LKQ6kTTHnhO6xCzC9z0mXnPS_ORXZmz8nfBT9CqYAb4-AydYEl8xgff7N8RJzo_ZGzYHLpVTun_Q6TqlEmP8_wE8hyq94</recordid><startdate>20101201</startdate><enddate>20101201</enddate><creator>Ingraham, Susan E</creator><creator>Saha, Monalee</creator><creator>Carpenter, Ashley R</creator><creator>Robinson, Melissa</creator><creator>Ismail, Ihab</creator><creator>Singh, Sunita</creator><creator>Hains, David</creator><creator>Robinson, Michael L</creator><creator>Hirselj, Daniel A</creator><creator>Koff, Stephen A</creator><creator>Bates, Carlton M</creator><creator>McHugh, Kirk M</creator><general>Nature Publishing Group US</general><general>Lippincott Williams & Wilkins</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20101201</creationdate><title>Pathogenesis of Renal Injury in the Megabladder Mouse: A Genetic Model of Congenital Obstructive Nephropathy</title><author>Ingraham, Susan E ; Saha, Monalee ; Carpenter, Ashley R ; Robinson, Melissa ; Ismail, Ihab ; Singh, Sunita ; Hains, David ; Robinson, Michael L ; Hirselj, Daniel A ; Koff, Stephen A ; Bates, Carlton M ; McHugh, Kirk M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-4104ce9af981325f5af4c745b8b19faee634acbc614c1f4942037d930efdf1dd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>basic-science-investigation</topic><topic>Biological and medical sciences</topic><topic>Child</topic><topic>Cystostomy</topic><topic>Disease Models, Animal</topic><topic>Disease Progression</topic><topic>Fibrosis</topic><topic>General aspects</topic><topic>Humans</topic><topic>Hydronephrosis - complications</topic><topic>Hydronephrosis - congenital</topic><topic>Hydronephrosis - pathology</topic><topic>Hydronephrosis - surgery</topic><topic>Kidney - diagnostic imaging</topic><topic>Kidney - injuries</topic><topic>Kidney - pathology</topic><topic>Kidney Failure, Chronic - congenital</topic><topic>Kidney Failure, Chronic - etiology</topic><topic>Kidney Failure, Chronic - pathology</topic><topic>Kidney Failure, Chronic - surgery</topic><topic>Kidneys</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mice, Mutant Strains</topic><topic>Nephritis, Interstitial - complications</topic><topic>Nephritis, Interstitial - congenital</topic><topic>Nephritis, Interstitial - pathology</topic><topic>Nephritis, Interstitial - surgery</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Pediatric Surgery</topic><topic>Pediatrics</topic><topic>Ultrasonography</topic><topic>Urinary system involvement in other diseases. Miscellaneous</topic><topic>Urinary tract. Prostate gland</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ingraham, Susan E</creatorcontrib><creatorcontrib>Saha, Monalee</creatorcontrib><creatorcontrib>Carpenter, Ashley R</creatorcontrib><creatorcontrib>Robinson, Melissa</creatorcontrib><creatorcontrib>Ismail, Ihab</creatorcontrib><creatorcontrib>Singh, Sunita</creatorcontrib><creatorcontrib>Hains, David</creatorcontrib><creatorcontrib>Robinson, Michael L</creatorcontrib><creatorcontrib>Hirselj, Daniel A</creatorcontrib><creatorcontrib>Koff, Stephen A</creatorcontrib><creatorcontrib>Bates, Carlton M</creatorcontrib><creatorcontrib>McHugh, Kirk M</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Pediatric research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ingraham, Susan E</au><au>Saha, Monalee</au><au>Carpenter, Ashley R</au><au>Robinson, Melissa</au><au>Ismail, Ihab</au><au>Singh, Sunita</au><au>Hains, David</au><au>Robinson, Michael L</au><au>Hirselj, Daniel A</au><au>Koff, Stephen A</au><au>Bates, Carlton M</au><au>McHugh, Kirk M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pathogenesis of Renal Injury in the Megabladder Mouse: A Genetic Model of Congenital Obstructive Nephropathy</atitle><jtitle>Pediatric research</jtitle><stitle>Pediatr Res</stitle><addtitle>Pediatr Res</addtitle><date>2010-12-01</date><risdate>2010</risdate><volume>68</volume><issue>6</issue><spage>500</spage><epage>507</epage><pages>500-507</pages><issn>0031-3998</issn><eissn>1530-0447</eissn><coden>PEREBL</coden><abstract>Congenital obstructive nephropathy (CON) is the most common cause of chronic renal failure in children often leading to end-stage renal disease. The megabladder (
mgb
) mouse exhibits signs of urinary tract obstruction
in utero
resulting in the development of hydroureteronephrosis and progressive renal failure after birth. This study examined the development of progressive renal injury in homozygous
mgb
mice (
mgb−/−
). Renal ultrasound was used to stratify the disease state of
mgb−
/
−
mice, whereas surgical rescue was performed using vesicostomy. The progression of renal injury was characterized using a series of pathogenic markers including alpha smooth muscle isoactin (α-SMA), TGF-β1, connective tissue growth factor (CTGF), E-cadherin, F4/80, Wilm's tumor (WT)-1, and paired box gene (Pax) 2. This analysis indicated that
mgb−
/
−
mice are born with pathologic changes in kidney development that progressively worsen in direct correlation with the severity of hydronephrosis. The initiation and pattern of fibrotic development observed in
mgb−
/
−
kidneys appeared distinctive from previous animal models of obstruction. These observations suggest that the
mgb
mouse represents a unique small animal model for the study of CON.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>20736884</pmid><doi>10.1203/PDR.0b013e3181f82f15</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0031-3998 |
| ispartof | Pediatric research, 2010-12, Vol.68 (6), p.500-507 |
| issn | 0031-3998 1530-0447 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3121911 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals basic-science-investigation Biological and medical sciences Child Cystostomy Disease Models, Animal Disease Progression Fibrosis General aspects Humans Hydronephrosis - complications Hydronephrosis - congenital Hydronephrosis - pathology Hydronephrosis - surgery Kidney - diagnostic imaging Kidney - injuries Kidney - pathology Kidney Failure, Chronic - congenital Kidney Failure, Chronic - etiology Kidney Failure, Chronic - pathology Kidney Failure, Chronic - surgery Kidneys Male Medical sciences Medicine Medicine & Public Health Mice Mice, Knockout Mice, Mutant Strains Nephritis, Interstitial - complications Nephritis, Interstitial - congenital Nephritis, Interstitial - pathology Nephritis, Interstitial - surgery Nephrology. Urinary tract diseases Pediatric Surgery Pediatrics Ultrasonography Urinary system involvement in other diseases. Miscellaneous Urinary tract. Prostate gland |
| title | Pathogenesis of Renal Injury in the Megabladder Mouse: A Genetic Model of Congenital Obstructive Nephropathy |
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