Lamellipodin-Deficient Mice: A Model of Rectal Carcinoma.
During a survey of clinical rectal prolapse (RP) cases in the mouse population at MIT animal research facilities, a high incidence of RP in the lamellipodin knock-out strain, C57BL/6-Raph1tm1Fbg (Lpd-/-) was documented. Upon further investigation, the Lpd-/- colony was found to be infected with mult...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4821566?pdf=render |
| _version_ | 1818300694113812480 |
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| author | Cassandra L Miller Sureshkumar Muthupalani Zeli Shen Frauke Drees Zhongming Ge Yan Feng Xiaowei Chen Guanyu Gong Karan K Nagar Timothy C Wang Frank B Gertler James G Fox |
| author_facet | Cassandra L Miller Sureshkumar Muthupalani Zeli Shen Frauke Drees Zhongming Ge Yan Feng Xiaowei Chen Guanyu Gong Karan K Nagar Timothy C Wang Frank B Gertler James G Fox |
| author_sort | Cassandra L Miller |
| collection | DOAJ |
| description | During a survey of clinical rectal prolapse (RP) cases in the mouse population at MIT animal research facilities, a high incidence of RP in the lamellipodin knock-out strain, C57BL/6-Raph1tm1Fbg (Lpd-/-) was documented. Upon further investigation, the Lpd-/- colony was found to be infected with multiple endemic enterohepatic Helicobacter species (EHS). Lpd-/- mice, a transgenic mouse strain produced at MIT, have not previously shown a distinct immune phenotype and are not highly susceptible to other opportunistic infections. Predominantly male Lpd-/- mice with RP exhibited lesions consistent with invasive rectal carcinoma concomitant to clinically evident RP. Multiple inflammatory cytokines, CD11b+Gr1+ myeloid-derived suppressor cell (MDSC) populations, and epithelial cells positive for a DNA damage biomarker, H2AX, were elevated in affected tissue, supporting their role in the neoplastic process. An evaluation of Lpd-/- mice with RP compared to EHS-infected, but clinically normal (CN) Lpd-/- animals indicated that all of these mice exhibit some degree of lower bowel inflammation; however, mice with prolapses had significantly higher degree of focal lesions at the colo-rectal junction. When Helicobacter spp. infections were eliminated in Lpd-/- mice by embryo transfer rederivation, the disease phenotype was abrogated, implicating EHS as a contributing factor in the development of rectal carcinoma. Here we describe lesions in Lpd-/- male mice consistent with a focal inflammation-induced neoplastic transformation and propose this strain as a mouse model of rectal carcinoma. |
| first_indexed | 2024-12-13T05:11:11Z |
| format | Article |
| id | doaj.art-ad22e9c5cf4e4321895699365f2a53f2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T05:11:11Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ad22e9c5cf4e4321895699365f2a53f22022-12-21T23:58:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01114e015294010.1371/journal.pone.0152940Lamellipodin-Deficient Mice: A Model of Rectal Carcinoma.Cassandra L MillerSureshkumar MuthupalaniZeli ShenFrauke DreesZhongming GeYan FengXiaowei ChenGuanyu GongKaran K NagarTimothy C WangFrank B GertlerJames G FoxDuring a survey of clinical rectal prolapse (RP) cases in the mouse population at MIT animal research facilities, a high incidence of RP in the lamellipodin knock-out strain, C57BL/6-Raph1tm1Fbg (Lpd-/-) was documented. Upon further investigation, the Lpd-/- colony was found to be infected with multiple endemic enterohepatic Helicobacter species (EHS). Lpd-/- mice, a transgenic mouse strain produced at MIT, have not previously shown a distinct immune phenotype and are not highly susceptible to other opportunistic infections. Predominantly male Lpd-/- mice with RP exhibited lesions consistent with invasive rectal carcinoma concomitant to clinically evident RP. Multiple inflammatory cytokines, CD11b+Gr1+ myeloid-derived suppressor cell (MDSC) populations, and epithelial cells positive for a DNA damage biomarker, H2AX, were elevated in affected tissue, supporting their role in the neoplastic process. An evaluation of Lpd-/- mice with RP compared to EHS-infected, but clinically normal (CN) Lpd-/- animals indicated that all of these mice exhibit some degree of lower bowel inflammation; however, mice with prolapses had significantly higher degree of focal lesions at the colo-rectal junction. When Helicobacter spp. infections were eliminated in Lpd-/- mice by embryo transfer rederivation, the disease phenotype was abrogated, implicating EHS as a contributing factor in the development of rectal carcinoma. Here we describe lesions in Lpd-/- male mice consistent with a focal inflammation-induced neoplastic transformation and propose this strain as a mouse model of rectal carcinoma.http://europepmc.org/articles/PMC4821566?pdf=render |
| spellingShingle | Cassandra L Miller Sureshkumar Muthupalani Zeli Shen Frauke Drees Zhongming Ge Yan Feng Xiaowei Chen Guanyu Gong Karan K Nagar Timothy C Wang Frank B Gertler James G Fox Lamellipodin-Deficient Mice: A Model of Rectal Carcinoma. PLoS ONE |
| title | Lamellipodin-Deficient Mice: A Model of Rectal Carcinoma. |
| title_full | Lamellipodin-Deficient Mice: A Model of Rectal Carcinoma. |
| title_fullStr | Lamellipodin-Deficient Mice: A Model of Rectal Carcinoma. |
| title_full_unstemmed | Lamellipodin-Deficient Mice: A Model of Rectal Carcinoma. |
| title_short | Lamellipodin-Deficient Mice: A Model of Rectal Carcinoma. |
| title_sort | lamellipodin deficient mice a model of rectal carcinoma |
| url | http://europepmc.org/articles/PMC4821566?pdf=render |
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