Year: 2016
Type: article
Abstract: 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.
Source: PLoS ONE
Authors: 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
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: Biomedical Research Training for Veterinary Scientists, G2201867625, G2360436881, MIT Center for Environmental Health Sciences, G4774430914, Biophysical Regulation of Breast Differentiation, Diagnosis and Pathobiology of Emerging Enterohepatic Helicobacter spp. in Mice, G8093924085, G9000300833, Cancer Center Support (Core) Grant
OpenAlex ID: W2332417153