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Tissue specific loss of A-type lamins in the gastrointestinal epithelium can enhance polyp size.
Differentiation. 2015 Jan-Feb; 89(1-2):11-21.D

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+Show Affiliations

Developmental and Regenerative Biology, Institute of Medical Biology, 8A Biomedical Grove, 138648, Singapore; Department of Biological Sciences, NUS, Singapore.Center for Advanced Preclinical Research, Science Applications International Corporation-Frederick, Frederick, MD 21702, United States.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.Developmental and Regenerative Biology, Institute of Medical Biology, 8A Biomedical Grove, 138648, Singapore.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25578479

Citation

Wang, Audrey S., et al. "Tissue Specific Loss of A-type Lamins in the Gastrointestinal Epithelium Can Enhance Polyp Size." Differentiation; Research in Biological Diversity, vol. 89, no. 1-2, 2015, pp. 11-21.
Wang AS, Kozlov SV, Stewart CL, et al. Tissue specific loss of A-type lamins in the gastrointestinal epithelium can enhance polyp size. Differentiation. 2015;89(1-2):11-21.
Wang, A. S., Kozlov, S. V., Stewart, C. L., & Horn, H. F. (2015). Tissue specific loss of A-type lamins in the gastrointestinal epithelium can enhance polyp size. Differentiation; Research in Biological Diversity, 89(1-2), 11-21. https://doi.org/10.1016/j.diff.2014.12.002
Wang AS, et al. Tissue Specific Loss of A-type Lamins in the Gastrointestinal Epithelium Can Enhance Polyp Size. Differentiation. 2015 Jan-Feb;89(1-2):11-21. PubMed PMID: 25578479.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tissue specific loss of A-type lamins in the gastrointestinal epithelium can enhance polyp size. AU - Wang,Audrey S, AU - Kozlov,Serguei V, AU - Stewart,Colin L, AU - Horn,Henning F, Y1 - 2015/01/08/ PY - 2014/09/08/received PY - 2014/12/08/revised PY - 2014/12/17/accepted PY - 2015/1/13/entrez PY - 2015/1/13/pubmed PY - 2016/1/9/medline KW - Gastrointestinal cancer KW - Lamins KW - Lgr5 KW - LoxP KW - Villin-Cre SP - 11 EP - 21 JF - Differentiation; research in biological diversity JO - Differentiation VL - 89 IS - 1-2 N2 - 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. SN - 1432-0436 UR - https://www.unboundmedicine.com/medline/citation/25578479/Tissue_specific_loss_of_A_type_lamins_in_the_gastrointestinal_epithelium_can_enhance_polyp_size_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0301-4681(14)00097-8 DB - PRIME DP - Unbound Medicine ER -