Differences in renal cortex transcriptional profiling of wild-type and novel type B cystinuria model rats
Cystinuria is a genetic disorder of cystine transport that accounts for 1–2% of all cases of renal lithiasis. It is characterized by hyperexcretion of cystine in urine and recurrent cystine lithiasis. Defective transport of cystine into epithelial cells of renal tubules occurs because of mutations o...
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| Veröffentlicht in: | Urolithiasis 2022-06, Vol.50 (3), p.279-291 |
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| creator | Zhang, Zihan Zheng, Rui Chen, Zhoutong Zhan, Xia Fang, Xiaoliang Liu, Meizhen Li, Yongmei Xu, Yonghu Li, Dali Geng, Hongquan Zhang, Xiaohui Xu, Guofeng |
| description | Cystinuria is a genetic disorder of cystine transport that accounts for 1–2% of all cases of renal lithiasis. It is characterized by hyperexcretion of cystine in urine and recurrent cystine lithiasis. Defective transport of cystine into epithelial cells of renal tubules occurs because of mutations of the transport heterodimer, including protein b
0,+
AT (encoded by SLC7A9) and rBAT (encoded by SLC3A1) linked through a covalent disulfide bond. Study generated a novel type B cystinuria rat model by artificially deleting 7 bp of
Slc7a9
gene exon 3 using the CRISPR-Cas9 system, and those
Slc7a9
-deficient rats were proved to be similar with cystinuria in terms of genome, transcriptome, translation, and biologic phenotypes with no off-target editing. Subsequent comparisons of renal histopathology indicated model rats gained typical secondary changes as medullary fibrosis with no stone formation. A total of 689 DEGs (383 upregulated and 306 downregulated) were differentially expressed in the renal cortex of cystinuria rats. In accordance with the functional annotation of DEGs, the potential role of glutathione metabolism processes in the kidney of cystinuria rat model was proposed, and KEGG analysis results showed that knock-out of
Slc7a9
gene triggered more biological changes which has not been studied. In short, for the first time, a rat model and its transcriptional database that mimics the pathogenesis and clinical consequences of human type B cystinuria were generated. |
| doi_str_mv | 10.1007/s00240-022-01321-6 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9110498</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2664956654</sourcerecordid><originalsourceid>FETCH-LOGICAL-c355t-38eb4117c2c6b6330611680e993677b2657ce78fe76a3bbb04fdc71a9e8f11ad3</originalsourceid><addsrcrecordid>eNp9kU1PHDEMhqOqVUGUP8ChitQLlyn5mmRyQSrQDySkXso5ymScbdBsMiQzwP77ZllKaQ_NJY792LH9InREyUdKiDophDBBGsJYQyhntJGv0D6jWjSKcfn6hb2HDku5IfVorQUlb9EebwWVQvN9FC6C95AhOig4RFwtO2KX8gwPeM42FpfDNIe0dU85-TCGuMLJ4_swDs28mQDbOOCY7mDEj88z7DZlDnHJweJ1Gqo_27m8Q2-8HQscPt0H6PrL5x_n35qr718vzz9dNY637dzwDnpBqXLMyV5yTiSlsiOgNZdK9Uy2yoHqPChped_3RPjBKWo1dJ5SO_ADdLqrOy39GgYHsY4xmimHtc0bk2wwf0di-GlW6c5oSonQXS1w_FQgp9sFymzWoTgYRxshLcWwujmtVW2yoh_-QW_SkuuqtlTFWilbUSm2o1xOpWTwz81QYrZimp2YpoppHsU0sia9fznGc8pv6SrAd0CpobiC_Ofv_5T9BRHXq5I</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2664956654</pqid></control><display><type>article</type><title>Differences in renal cortex transcriptional profiling of wild-type and novel type B cystinuria model rats</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Zhang, Zihan ; Zheng, Rui ; Chen, Zhoutong ; Zhan, Xia ; Fang, Xiaoliang ; Liu, Meizhen ; Li, Yongmei ; Xu, Yonghu ; Li, Dali ; Geng, Hongquan ; Zhang, Xiaohui ; Xu, Guofeng</creator><creatorcontrib>Zhang, Zihan ; Zheng, Rui ; Chen, Zhoutong ; Zhan, Xia ; Fang, Xiaoliang ; Liu, Meizhen ; Li, Yongmei ; Xu, Yonghu ; Li, Dali ; Geng, Hongquan ; Zhang, Xiaohui ; Xu, Guofeng</creatorcontrib><description>Cystinuria is a genetic disorder of cystine transport that accounts for 1–2% of all cases of renal lithiasis. It is characterized by hyperexcretion of cystine in urine and recurrent cystine lithiasis. Defective transport of cystine into epithelial cells of renal tubules occurs because of mutations of the transport heterodimer, including protein b
0,+
AT (encoded by SLC7A9) and rBAT (encoded by SLC3A1) linked through a covalent disulfide bond. Study generated a novel type B cystinuria rat model by artificially deleting 7 bp of
Slc7a9
gene exon 3 using the CRISPR-Cas9 system, and those
Slc7a9
-deficient rats were proved to be similar with cystinuria in terms of genome, transcriptome, translation, and biologic phenotypes with no off-target editing. Subsequent comparisons of renal histopathology indicated model rats gained typical secondary changes as medullary fibrosis with no stone formation. A total of 689 DEGs (383 upregulated and 306 downregulated) were differentially expressed in the renal cortex of cystinuria rats. In accordance with the functional annotation of DEGs, the potential role of glutathione metabolism processes in the kidney of cystinuria rat model was proposed, and KEGG analysis results showed that knock-out of
Slc7a9
gene triggered more biological changes which has not been studied. In short, for the first time, a rat model and its transcriptional database that mimics the pathogenesis and clinical consequences of human type B cystinuria were generated.</description><identifier>ISSN: 2194-7236</identifier><identifier>ISSN: 2194-7228</identifier><identifier>EISSN: 2194-7236</identifier><identifier>DOI: 10.1007/s00240-022-01321-6</identifier><identifier>PMID: 35416493</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Amino Acid Transport Systems, Basic - genetics ; Amino Acid Transport Systems, Basic - metabolism ; Animals ; Chemical bonds ; CRISPR ; Cystine - metabolism ; Cystinuria - genetics ; Cystinuria - metabolism ; Embryos ; Female ; Hospitals ; Humans ; Laboratories ; Lithiasis - complications ; Male ; Medical Biochemistry ; Medicine ; Medicine & Public Health ; Metabolism ; Mutation ; Nephrology ; Original ; Original Article ; Pediatrics ; Proteins ; Rats ; Rodents ; Urinary tract diseases ; Urine ; Urology</subject><ispartof>Urolithiasis, 2022-06, Vol.50 (3), p.279-291</ispartof><rights>The Author(s) 2022</rights><rights>2022. The Author(s).</rights><rights>The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c355t-38eb4117c2c6b6330611680e993677b2657ce78fe76a3bbb04fdc71a9e8f11ad3</cites><orcidid>0000-0002-5104-5386</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00240-022-01321-6$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00240-022-01321-6$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35416493$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Zihan</creatorcontrib><creatorcontrib>Zheng, Rui</creatorcontrib><creatorcontrib>Chen, Zhoutong</creatorcontrib><creatorcontrib>Zhan, Xia</creatorcontrib><creatorcontrib>Fang, Xiaoliang</creatorcontrib><creatorcontrib>Liu, Meizhen</creatorcontrib><creatorcontrib>Li, Yongmei</creatorcontrib><creatorcontrib>Xu, Yonghu</creatorcontrib><creatorcontrib>Li, Dali</creatorcontrib><creatorcontrib>Geng, Hongquan</creatorcontrib><creatorcontrib>Zhang, Xiaohui</creatorcontrib><creatorcontrib>Xu, Guofeng</creatorcontrib><title>Differences in renal cortex transcriptional profiling of wild-type and novel type B cystinuria model rats</title><title>Urolithiasis</title><addtitle>Urolithiasis</addtitle><addtitle>Urolithiasis</addtitle><description>Cystinuria is a genetic disorder of cystine transport that accounts for 1–2% of all cases of renal lithiasis. It is characterized by hyperexcretion of cystine in urine and recurrent cystine lithiasis. Defective transport of cystine into epithelial cells of renal tubules occurs because of mutations of the transport heterodimer, including protein b
0,+
AT (encoded by SLC7A9) and rBAT (encoded by SLC3A1) linked through a covalent disulfide bond. Study generated a novel type B cystinuria rat model by artificially deleting 7 bp of
Slc7a9
gene exon 3 using the CRISPR-Cas9 system, and those
Slc7a9
-deficient rats were proved to be similar with cystinuria in terms of genome, transcriptome, translation, and biologic phenotypes with no off-target editing. Subsequent comparisons of renal histopathology indicated model rats gained typical secondary changes as medullary fibrosis with no stone formation. A total of 689 DEGs (383 upregulated and 306 downregulated) were differentially expressed in the renal cortex of cystinuria rats. In accordance with the functional annotation of DEGs, the potential role of glutathione metabolism processes in the kidney of cystinuria rat model was proposed, and KEGG analysis results showed that knock-out of
Slc7a9
gene triggered more biological changes which has not been studied. In short, for the first time, a rat model and its transcriptional database that mimics the pathogenesis and clinical consequences of human type B cystinuria were generated.</description><subject>Amino Acid Transport Systems, Basic - genetics</subject><subject>Amino Acid Transport Systems, Basic - metabolism</subject><subject>Animals</subject><subject>Chemical bonds</subject><subject>CRISPR</subject><subject>Cystine - metabolism</subject><subject>Cystinuria - genetics</subject><subject>Cystinuria - metabolism</subject><subject>Embryos</subject><subject>Female</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Laboratories</subject><subject>Lithiasis - complications</subject><subject>Male</subject><subject>Medical Biochemistry</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolism</subject><subject>Mutation</subject><subject>Nephrology</subject><subject>Original</subject><subject>Original Article</subject><subject>Pediatrics</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rodents</subject><subject>Urinary tract diseases</subject><subject>Urine</subject><subject>Urology</subject><issn>2194-7236</issn><issn>2194-7228</issn><issn>2194-7236</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kU1PHDEMhqOqVUGUP8ChitQLlyn5mmRyQSrQDySkXso5ymScbdBsMiQzwP77ZllKaQ_NJY792LH9InREyUdKiDophDBBGsJYQyhntJGv0D6jWjSKcfn6hb2HDku5IfVorQUlb9EebwWVQvN9FC6C95AhOig4RFwtO2KX8gwPeM42FpfDNIe0dU85-TCGuMLJ4_swDs28mQDbOOCY7mDEj88z7DZlDnHJweJ1Gqo_27m8Q2-8HQscPt0H6PrL5x_n35qr718vzz9dNY637dzwDnpBqXLMyV5yTiSlsiOgNZdK9Uy2yoHqPChped_3RPjBKWo1dJ5SO_ADdLqrOy39GgYHsY4xmimHtc0bk2wwf0di-GlW6c5oSonQXS1w_FQgp9sFymzWoTgYRxshLcWwujmtVW2yoh_-QW_SkuuqtlTFWilbUSm2o1xOpWTwz81QYrZimp2YpoppHsU0sia9fznGc8pv6SrAd0CpobiC_Ofv_5T9BRHXq5I</recordid><startdate>20220601</startdate><enddate>20220601</enddate><creator>Zhang, Zihan</creator><creator>Zheng, Rui</creator><creator>Chen, Zhoutong</creator><creator>Zhan, Xia</creator><creator>Fang, Xiaoliang</creator><creator>Liu, Meizhen</creator><creator>Li, Yongmei</creator><creator>Xu, Yonghu</creator><creator>Li, Dali</creator><creator>Geng, Hongquan</creator><creator>Zhang, Xiaohui</creator><creator>Xu, Guofeng</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5104-5386</orcidid></search><sort><creationdate>20220601</creationdate><title>Differences in renal cortex transcriptional profiling of wild-type and novel type B cystinuria model rats</title><author>Zhang, Zihan ; 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It is characterized by hyperexcretion of cystine in urine and recurrent cystine lithiasis. Defective transport of cystine into epithelial cells of renal tubules occurs because of mutations of the transport heterodimer, including protein b
0,+
AT (encoded by SLC7A9) and rBAT (encoded by SLC3A1) linked through a covalent disulfide bond. Study generated a novel type B cystinuria rat model by artificially deleting 7 bp of
Slc7a9
gene exon 3 using the CRISPR-Cas9 system, and those
Slc7a9
-deficient rats were proved to be similar with cystinuria in terms of genome, transcriptome, translation, and biologic phenotypes with no off-target editing. Subsequent comparisons of renal histopathology indicated model rats gained typical secondary changes as medullary fibrosis with no stone formation. A total of 689 DEGs (383 upregulated and 306 downregulated) were differentially expressed in the renal cortex of cystinuria rats. In accordance with the functional annotation of DEGs, the potential role of glutathione metabolism processes in the kidney of cystinuria rat model was proposed, and KEGG analysis results showed that knock-out of
Slc7a9
gene triggered more biological changes which has not been studied. In short, for the first time, a rat model and its transcriptional database that mimics the pathogenesis and clinical consequences of human type B cystinuria were generated.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>35416493</pmid><doi>10.1007/s00240-022-01321-6</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-5104-5386</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Transport Systems, Basic - genetics Amino Acid Transport Systems, Basic - metabolism Animals Chemical bonds CRISPR Cystine - metabolism Cystinuria - genetics Cystinuria - metabolism Embryos Female Hospitals Humans Laboratories Lithiasis - complications Male Medical Biochemistry Medicine Medicine & Public Health Metabolism Mutation Nephrology Original Original Article Pediatrics Proteins Rats Rodents Urinary tract diseases Urine Urology |
| title | Differences in renal cortex transcriptional profiling of wild-type and novel type B cystinuria model rats |
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