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Expression of growth regulatory genes in a SCID mouse-human model of intestinal epithelial regeneration

Lookup NU author(s): Abid Sattar, Professor Steve RobsonORCiD, Dr Brian Angus, Professor Frederick Campbell


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Analysis of human intestinal epithelial regeneration has been limited. This study has used a novel SCID mouse-human model to test the hypothesis that distinct stages of human intestinal epithelial regeneration are accompanied by differential expression of growth regulatory genes. Disaggregated epithelium, which included crypt cell aggregates, was isolated from human fetal small intestine and transplanted subcutaneously in SCID mice. This method induced a coordinated regeneration response and enabled temporal separation of cell populations at different stages of histogenesis and cytodifferentiation. Graft epithelium was identified using a specific anti-human monoclonal antibody (MAb 5D3) against cytokeratins 8 and 18. Functional epithelial lineages were identified by appropriate markers. Growth regulatory genes relevant to proliferation and apoptosis, including Bcl-2, p53 and Ki67, were assayed at different stages of regeneration. During early regeneration, Bcl-2, p53, and Ki67 were expressed throughout the epithelial compartment. On completion of regeneration, these genes were expressed only in crypt epithelium and were absent from villi. This study has established a novel SCID mouse-human model of intestinal epithelial regeneration. During early regeneration, increased Bcl-2 and Ki67 expression may indicate suppression of apoptosis and enhanced proliferation respectively, consistent with expansion of the stem cell fraction. The p53 gene may influence pathways of differentiation during regeneration, analogous to its role during development.

Publication metadata

Author(s): Sattar A, Robson SC, Patel HRH, Angus B, Campbell FC

Publication type: Article

Publication status: Published

Journal: Journal of Pathology

Year: 1999

Volume: 187

Issue: 2

Pages: 229-236

Print publication date: 01/01/1999

ISSN (print): 0022-3417

ISSN (electronic): 1096-9896

Publisher: John Wiley & Sons Ltd.


DOI: 10.1002/(SICI)1096-9896(199901)187:2<229::AID-PATH218>3.0.CO;2-8

PubMed id: 10365099


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