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PLoS One. 2016 Apr 5;11(4):e0152940. doi: 10.1371/journal.pone.0152940. eCollection 2016.

Lamellipodin-Deficient Mice: A Model of Rectal Carcinoma.

Author information

1
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, United States of America.
2
David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States of America.
3
Division of Digestive and Liver Diseases, Columbia University, New York, NY, United States of America.
4
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States of America.

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.

PMID:
27045955
PMCID:
PMC4821566
DOI:
10.1371/journal.pone.0152940
[Indexed for MEDLINE]
Free PMC Article

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