Tissue specific loss of A-type lamins in the gastrointestinal epithelium can enhance polyp size

Audrey S. Wang, Serguei V. Kozlov, Colin L. Stewart, Henning Horn

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 LmnaFL/FL (floxed). LmnaFL/FL was specifically deleted in the gastrointestinal (GI) epithelium by crossing the LmnaFL/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 (ApcMin/+) 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.

Original languageEnglish
Pages (from-to)11-21
Number of pages11
JournalDifferentiation
Volume89
Issue number1-2
DOIs
Publication statusPublished - 1 Jan 2015
Externally publishedYes

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Keywords

  • Gastrointestinal cancer
  • Lamins
  • Lgr5
  • LoxP
  • Villin-Cre

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology
  • Cancer Research
  • Medicine(all)

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