Lamellipodin-Deficient Mice: A Model of Rectal Carcinoma
Author(s)Chen, Xiaowei; Nagar, Karan K.; Wang, Timothy C.; Miller, Cassandra L.; Muthupalani, Sureshkumar; Shen, Zeli; Drees, Frauke; Ge, Zhongming; Feng, Yan; Gong, Guanyu; Gertler, Frank; Fox, James G; ... Show more Show less
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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-Raph1[superscript tm1Fbg] (Lpd[superscript -/-]) was documented. Upon further investigation, the Lpd[superscript -/-] colony was found to be infected with multiple endemic enterohepatic Helicobacter species (EHS). Lpd[superscript -/-] 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[superscript -/-] 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[superscript -/-] mice with RP compared to EHS-infected, but clinically normal (CN) Lpd[superscript -/-] 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[superscript -/-] 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[superscript -/-] male mice consistent with a focal inflammation-induced neoplastic transformation and propose this strain as a mouse model of rectal carcinoma.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Division of Comparative Medicine
Public Library of Science
Miller, Cassandra L.; Muthupalani, Sureshkumar; Shen, Zeli; Drees, Frauke; Ge, Zhongming; Feng, Yan; Chen, Xiaowei et al. “Lamellipodin-Deficient Mice: A Model of Rectal Carcinoma.” Edited by Sergei Grivennikov. PLoS ONE 11, no. 4 (April 2016): e0152940 © 2016 Miller et al.
Final published version