title: Tissue specific loss of A-type lamins in the gastrointestinal epithelium can enhance polyp size.
abstract: The nuclear lamina, comprised of the A and B-type lamins, is important in maintaining nuclear shape and in regulating key nuclear functions such as chromatin organization and transcription. Deletion of the A-type lamins results in genome instability and many cancers show altered levels of A-type lamin expression. Loss of function mutations in the mouse Lmna gene result in early postnatal lethality, usually within 3-5 weeks of birth making an analysis of the role of lamins in carcinogenesis difficult. To circumvent early lethality, and determine the role of the A-type lamins in specific tissues in older mice we derived a conditional allele of Lmna(FL/FL) (floxed). Lmna(FL/FL) was specifically deleted in the gastrointestinal (GI) epithelium by crossing the Lmna(FL/FL) mice with Villin-Cre mice. Mice lacking Lmna in the GI are overtly normal with no effects on overall growth, longevity or GI morphology. On a GI specific sensitized (Apc(Min/+)) background, polyp numbers are unchanged, but polyp size is slightly increased, and only in the duodenum. Our findings reveal that although A-type lamins are dispensable in the postnatal GI epithelium, loss of Lmna under malignant conditions may, to a limited extent, enhance polyp size indicating that A-type lamins may regulate cell proliferation in the transformed GI epithelium.
authors.affiliation: Developmental and Regenerative Biology, Institute of Medical Biology, 8A Biomedical Grove, 138648, Singapore; Department of Biological Sciences, NUS, Singapore.
authors.forename: Audrey S
authors.initials: AS
authors.lastname: Wang
authors.affiliation: Center for Advanced Preclinical Research, Science Applications International Corporation-Frederick, Frederick, MD 21702, United States.
authors.forename: Serguei V
authors.initials: SV
authors.lastname: Kozlov
authors.affiliation: Developmental and Regenerative Biology, Institute of Medical Biology, 8A Biomedical Grove, 138648, Singapore; Department of Biological Sciences, NUS, Singapore. Electronic address: colin.stewart@imb.a-star.edu.sg.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Stewart
authors.affiliation: Developmental and Regenerative Biology, Institute of Medical Biology, 8A Biomedical Grove, 138648, Singapore.
authors.forename: Henning F
authors.initials: HF
authors.lastname: Horn
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004848:Epithelium / Q000254:growth & development / Q000473:pathology; D041981:Gastrointestinal Tract / Q000254:growth & development / Q000473:pathology; D042822:Genomic Instability; D007417:Intestinal Polyps / Q000235:genetics* / Q000473:pathology; D034904:Lamin Type A / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009928:Organ Specificity
chemical_list: D034904:Lamin Type A; C576142:Lmna protein, mouse
keywords: Gastrointestinal cancer; Lamins; Lgr5; LoxP; Villin-Cre