Pdx1 inactivation restricted to the intestinal epithelium in mice alters duodenal gene expression in enterocytes and enteroendocrine cells
Null mutant mice lacking the transcription factor pancreatic and duodenal homeobox 1 (Pdx1) are apancreatic and survive only a few days after birth. The role of Pdx1 in regulating intestinal gene expression has therefore yet to be determined in viable mice with normal pancreatic development. We hypo...
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| Veröffentlicht in: | American journal of physiology: Gastrointestinal and liver physiology 2009-12, Vol.297 (6), p.G1126-G1137 |
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| creator | Chen, Chin Fang, Rixun Davis, Corrine Maravelias, Charalambos Sibley, Eric |
| description | Null mutant mice lacking the transcription factor pancreatic and duodenal homeobox 1 (Pdx1) are apancreatic and survive only a few days after birth. The role of Pdx1 in regulating intestinal gene expression has therefore yet to be determined in viable mice with normal pancreatic development. We hypothesized that conditional inactivation of Pdx1 restricted to the intestinal epithelium would alter intestinal gene expression and cell differentiation. Pdx1(flox/flox);VilCre mice with intestine-specific Pdx1 inactivation were generated by crossing a transgenic mouse strain expressing Cre recombinase, driven by a mouse villin 1 gene promoter fragment, with a mutant mouse strain homozygous for loxP site-flanked Pdx1. Pdx1 protein is undetectable in all epithelial cells in the intestinal epithelium of Pdx1(flox/flox);VilCre mice. Goblet cell number and mRNA abundance for mucin 3 and mucin 13 genes in the proximal small intestine are comparable between Pdx1(flox/flox);VilCre and control mice. Similarly, Paneth cell number and expression of Paneth cell-related genes Defa1, Defcr-rs1, and Mmp7 in the proximal small intestine remain statistically unchanged by Pdx1 inactivation. Although the number of enteroendocrine cells expressing chromogranin A/B, gastric inhibitory polypeptide (Gip), or somatostatin (Sst) is unaffected in the Pdx1(flox/flox);VilCre mice, mRNA abundance for Gip and Sst is significantly reduced in the proximal small intestine. Conditional Pdx1 inactivation attenuates intestinal alkaline phosphatase (IAP) activity in the duodenal epithelium, consistent with an average 91% decrease in expression of the mouse enterocyte IAP gene, alkaline phosphatase 3 (a novel Pdx1 target candidate), in the proximal small intestine following Pdx1 inactivation. We conclude that Pdx1 is necessary for patterning appropriate gene expression in enterocytes and enteroendocrine cells of the proximal small intestine. |
| doi_str_mv | 10.1152/ajpgi.90586.2008 |
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The role of Pdx1 in regulating intestinal gene expression has therefore yet to be determined in viable mice with normal pancreatic development. We hypothesized that conditional inactivation of Pdx1 restricted to the intestinal epithelium would alter intestinal gene expression and cell differentiation. Pdx1(flox/flox);VilCre mice with intestine-specific Pdx1 inactivation were generated by crossing a transgenic mouse strain expressing Cre recombinase, driven by a mouse villin 1 gene promoter fragment, with a mutant mouse strain homozygous for loxP site-flanked Pdx1. Pdx1 protein is undetectable in all epithelial cells in the intestinal epithelium of Pdx1(flox/flox);VilCre mice. Goblet cell number and mRNA abundance for mucin 3 and mucin 13 genes in the proximal small intestine are comparable between Pdx1(flox/flox);VilCre and control mice. Similarly, Paneth cell number and expression of Paneth cell-related genes Defa1, Defcr-rs1, and Mmp7 in the proximal small intestine remain statistically unchanged by Pdx1 inactivation. Although the number of enteroendocrine cells expressing chromogranin A/B, gastric inhibitory polypeptide (Gip), or somatostatin (Sst) is unaffected in the Pdx1(flox/flox);VilCre mice, mRNA abundance for Gip and Sst is significantly reduced in the proximal small intestine. Conditional Pdx1 inactivation attenuates intestinal alkaline phosphatase (IAP) activity in the duodenal epithelium, consistent with an average 91% decrease in expression of the mouse enterocyte IAP gene, alkaline phosphatase 3 (a novel Pdx1 target candidate), in the proximal small intestine following Pdx1 inactivation. We conclude that Pdx1 is necessary for patterning appropriate gene expression in enterocytes and enteroendocrine cells of the proximal small intestine.</description><identifier>ISSN: 0193-1857</identifier><identifier>EISSN: 1522-1547</identifier><identifier>DOI: 10.1152/ajpgi.90586.2008</identifier><identifier>PMID: 19808654</identifier><identifier>CODEN: APGPDF</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>Animals ; Cell Differentiation ; Cells ; Duodenum - metabolism ; Enterocytes - metabolism ; Enteroendocrine Cells - metabolism ; Gene expression ; Gene Expression Regulation ; Genes ; Goblet Cells - metabolism ; Homeodomain Proteins - genetics ; Integrases - genetics ; Intestinal Mucosa - metabolism ; Mice ; Mice, Mutant Strains ; Mice, Transgenic ; Microfilament Proteins - genetics ; Mucosal Biology ; Mutation ; Paneth Cells - metabolism ; Promoter Regions, Genetic ; Ribonucleic acid ; RNA ; RNA, Messenger - metabolism ; Rodents ; Small intestine ; Trans-Activators - deficiency ; Trans-Activators - genetics</subject><ispartof>American journal of physiology: Gastrointestinal and liver physiology, 2009-12, Vol.297 (6), p.G1126-G1137</ispartof><rights>Copyright American Physiological Society Dec 2009</rights><rights>Copyright © 2009 the American Physiological Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c380t-3e2653e3189dd7dca24bb207dfc8fb70a5a1a110501174286a64d045ca6a71233</citedby><cites>FETCH-LOGICAL-c380t-3e2653e3189dd7dca24bb207dfc8fb70a5a1a110501174286a64d045ca6a71233</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3039,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19808654$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Chin</creatorcontrib><creatorcontrib>Fang, Rixun</creatorcontrib><creatorcontrib>Davis, Corrine</creatorcontrib><creatorcontrib>Maravelias, Charalambos</creatorcontrib><creatorcontrib>Sibley, Eric</creatorcontrib><title>Pdx1 inactivation restricted to the intestinal epithelium in mice alters duodenal gene expression in enterocytes and enteroendocrine cells</title><title>American journal of physiology: Gastrointestinal and liver physiology</title><addtitle>Am J Physiol Gastrointest Liver Physiol</addtitle><description>Null mutant mice lacking the transcription factor pancreatic and duodenal homeobox 1 (Pdx1) are apancreatic and survive only a few days after birth. The role of Pdx1 in regulating intestinal gene expression has therefore yet to be determined in viable mice with normal pancreatic development. We hypothesized that conditional inactivation of Pdx1 restricted to the intestinal epithelium would alter intestinal gene expression and cell differentiation. Pdx1(flox/flox);VilCre mice with intestine-specific Pdx1 inactivation were generated by crossing a transgenic mouse strain expressing Cre recombinase, driven by a mouse villin 1 gene promoter fragment, with a mutant mouse strain homozygous for loxP site-flanked Pdx1. Pdx1 protein is undetectable in all epithelial cells in the intestinal epithelium of Pdx1(flox/flox);VilCre mice. Goblet cell number and mRNA abundance for mucin 3 and mucin 13 genes in the proximal small intestine are comparable between Pdx1(flox/flox);VilCre and control mice. Similarly, Paneth cell number and expression of Paneth cell-related genes Defa1, Defcr-rs1, and Mmp7 in the proximal small intestine remain statistically unchanged by Pdx1 inactivation. Although the number of enteroendocrine cells expressing chromogranin A/B, gastric inhibitory polypeptide (Gip), or somatostatin (Sst) is unaffected in the Pdx1(flox/flox);VilCre mice, mRNA abundance for Gip and Sst is significantly reduced in the proximal small intestine. Conditional Pdx1 inactivation attenuates intestinal alkaline phosphatase (IAP) activity in the duodenal epithelium, consistent with an average 91% decrease in expression of the mouse enterocyte IAP gene, alkaline phosphatase 3 (a novel Pdx1 target candidate), in the proximal small intestine following Pdx1 inactivation. We conclude that Pdx1 is necessary for patterning appropriate gene expression in enterocytes and enteroendocrine cells of the proximal small intestine.</description><subject>Animals</subject><subject>Cell Differentiation</subject><subject>Cells</subject><subject>Duodenum - metabolism</subject><subject>Enterocytes - metabolism</subject><subject>Enteroendocrine Cells - metabolism</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Genes</subject><subject>Goblet Cells - metabolism</subject><subject>Homeodomain Proteins - genetics</subject><subject>Integrases - genetics</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Mice</subject><subject>Mice, Mutant Strains</subject><subject>Mice, Transgenic</subject><subject>Microfilament Proteins - genetics</subject><subject>Mucosal Biology</subject><subject>Mutation</subject><subject>Paneth Cells - metabolism</subject><subject>Promoter Regions, Genetic</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Messenger - metabolism</subject><subject>Rodents</subject><subject>Small intestine</subject><subject>Trans-Activators - deficiency</subject><subject>Trans-Activators - genetics</subject><issn>0193-1857</issn><issn>1522-1547</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1v1DAQhi0EokvhzglZXDhlmbHjxLkgoap8SJXgAGfLa89uvUriYCdV-xf41Tjtiq-T5XeeeTUzL2MvEbaISry1x-kQth0o3WwFgH7ENkUWFaq6fcw2gJ2sUKv2jD3L-QgASiA-ZWfYadCNqjfs51d_izyM1s3hxs4hjjxRnlNwM3k-Rz5fUynPRStQz2kKRenDMhSVD8ERt_1MKXO_RE8rcqCRON1OxSevfoWjYpCiuys23I7-9KfRR5dCoR31fX7Onuxtn-nF6T1n3z9cfrv4VF19-fj54v1V5aSGuZIkGiVJou68b72zot7tBLR-7_R-14JVFi0iKEBsa6Eb29QeauVsY1sUUp6zdw--07IbyLsyTLK9mVIYbLoz0Qbzb2UM1-YQb4zQCqCri8Gbk0GKP5ZyGTOEvK5gR4pLNq2UDUihdSFf_0ce45LKkbIRUpTUoMECwQPkUsw50f73KAhmjdncx2zuYzZrzKXl1d8r_Gk45Sp_AZLGqDs</recordid><startdate>20091201</startdate><enddate>20091201</enddate><creator>Chen, Chin</creator><creator>Fang, Rixun</creator><creator>Davis, Corrine</creator><creator>Maravelias, Charalambos</creator><creator>Sibley, Eric</creator><general>American Physiological Society</general><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>20091201</creationdate><title>Pdx1 inactivation restricted to the intestinal epithelium in mice alters duodenal gene expression in enterocytes and enteroendocrine cells</title><author>Chen, Chin ; Fang, Rixun ; Davis, Corrine ; Maravelias, Charalambos ; Sibley, Eric</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c380t-3e2653e3189dd7dca24bb207dfc8fb70a5a1a110501174286a64d045ca6a71233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Cell Differentiation</topic><topic>Cells</topic><topic>Duodenum - metabolism</topic><topic>Enterocytes - metabolism</topic><topic>Enteroendocrine Cells - metabolism</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Genes</topic><topic>Goblet Cells - metabolism</topic><topic>Homeodomain Proteins - genetics</topic><topic>Integrases - genetics</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Mice</topic><topic>Mice, Mutant Strains</topic><topic>Mice, Transgenic</topic><topic>Microfilament Proteins - genetics</topic><topic>Mucosal Biology</topic><topic>Mutation</topic><topic>Paneth Cells - metabolism</topic><topic>Promoter Regions, Genetic</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Messenger - metabolism</topic><topic>Rodents</topic><topic>Small intestine</topic><topic>Trans-Activators - deficiency</topic><topic>Trans-Activators - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Chin</creatorcontrib><creatorcontrib>Fang, Rixun</creatorcontrib><creatorcontrib>Davis, Corrine</creatorcontrib><creatorcontrib>Maravelias, Charalambos</creatorcontrib><creatorcontrib>Sibley, Eric</creatorcontrib><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>American journal of physiology: Gastrointestinal and liver physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Chin</au><au>Fang, Rixun</au><au>Davis, Corrine</au><au>Maravelias, Charalambos</au><au>Sibley, Eric</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pdx1 inactivation restricted to the intestinal epithelium in mice alters duodenal gene expression in enterocytes and enteroendocrine cells</atitle><jtitle>American journal of physiology: Gastrointestinal and liver physiology</jtitle><addtitle>Am J Physiol Gastrointest Liver Physiol</addtitle><date>2009-12-01</date><risdate>2009</risdate><volume>297</volume><issue>6</issue><spage>G1126</spage><epage>G1137</epage><pages>G1126-G1137</pages><issn>0193-1857</issn><eissn>1522-1547</eissn><coden>APGPDF</coden><abstract>Null mutant mice lacking the transcription factor pancreatic and duodenal homeobox 1 (Pdx1) are apancreatic and survive only a few days after birth. The role of Pdx1 in regulating intestinal gene expression has therefore yet to be determined in viable mice with normal pancreatic development. We hypothesized that conditional inactivation of Pdx1 restricted to the intestinal epithelium would alter intestinal gene expression and cell differentiation. Pdx1(flox/flox);VilCre mice with intestine-specific Pdx1 inactivation were generated by crossing a transgenic mouse strain expressing Cre recombinase, driven by a mouse villin 1 gene promoter fragment, with a mutant mouse strain homozygous for loxP site-flanked Pdx1. Pdx1 protein is undetectable in all epithelial cells in the intestinal epithelium of Pdx1(flox/flox);VilCre mice. Goblet cell number and mRNA abundance for mucin 3 and mucin 13 genes in the proximal small intestine are comparable between Pdx1(flox/flox);VilCre and control mice. Similarly, Paneth cell number and expression of Paneth cell-related genes Defa1, Defcr-rs1, and Mmp7 in the proximal small intestine remain statistically unchanged by Pdx1 inactivation. Although the number of enteroendocrine cells expressing chromogranin A/B, gastric inhibitory polypeptide (Gip), or somatostatin (Sst) is unaffected in the Pdx1(flox/flox);VilCre mice, mRNA abundance for Gip and Sst is significantly reduced in the proximal small intestine. Conditional Pdx1 inactivation attenuates intestinal alkaline phosphatase (IAP) activity in the duodenal epithelium, consistent with an average 91% decrease in expression of the mouse enterocyte IAP gene, alkaline phosphatase 3 (a novel Pdx1 target candidate), in the proximal small intestine following Pdx1 inactivation. We conclude that Pdx1 is necessary for patterning appropriate gene expression in enterocytes and enteroendocrine cells of the proximal small intestine.</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>19808654</pmid><doi>10.1152/ajpgi.90586.2008</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Cell Differentiation Cells Duodenum - metabolism Enterocytes - metabolism Enteroendocrine Cells - metabolism Gene expression Gene Expression Regulation Genes Goblet Cells - metabolism Homeodomain Proteins - genetics Integrases - genetics Intestinal Mucosa - metabolism Mice Mice, Mutant Strains Mice, Transgenic Microfilament Proteins - genetics Mucosal Biology Mutation Paneth Cells - metabolism Promoter Regions, Genetic Ribonucleic acid RNA RNA, Messenger - metabolism Rodents Small intestine Trans-Activators - deficiency Trans-Activators - genetics |
| title | Pdx1 inactivation restricted to the intestinal epithelium in mice alters duodenal gene expression in enterocytes and enteroendocrine cells |
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