title: Lamellipodin-Deficient Mice: A Model of Rectal Carcinoma.
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.
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, United States of America.
authors.forename: Cassandra L
authors.initials: CL
authors.lastname: Miller
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, United States of America.
authors.forename: Sureshkumar
authors.initials: S
authors.lastname: Muthupalani
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, United States of America.
authors.forename: Zeli
authors.initials: Z
authors.lastname: Shen
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States of America.
authors.forename: Frauke
authors.initials: F
authors.lastname: Drees
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, United States of America.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Ge
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, United States of America.
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Division of Digestive and Liver Diseases, Columbia University, New York, NY, United States of America.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States of America.
authors.forename: Guanyu
authors.initials: G
authors.lastname: Gong
authors.affiliation: Division of Digestive and Liver Diseases, Columbia University, New York, NY, United States of America.
authors.forename: Karan K
authors.initials: KK
authors.lastname: Nagar
authors.affiliation: Division of Digestive and Liver Diseases, Columbia University, New York, NY, United States of America.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Wang
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States of America.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Gertler
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, United States of America.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States of America.
authors.forename: James G
authors.initials: JG
authors.lastname: Fox
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D004249:DNA Damage; D004195:Disease Models, Animal; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; C493339:RAPH1 protein, human