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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.
•Derivation and characterization of a conditional (floxed) allele of the Lmna gene are described.•Mice with ubiquitous deletion of this allele die within 3 weeks of birth•Deletion of Lmna in the gut epithelium using Villin-Cre has no overt effect on growth or lifespan.•On a sensitized ApcMin/+ background LmnaFL/FL/Vil-Cre mice show increased polyp size in specific gut segments.•A-type lamins may regulate malignant cell proliferation in the gut epithelium.