National University of Singapore
UNDERSTANDING LAMIN A/C AND ITS ROLES IN DISEASE PATHOLOGIES
Abstract
dc:description.abstractTHE NUCLEAR LAMINA, COMPRISED OF THE A AND B-TYPE LAMINS, REGULATES CHROMATIN ORGANIZATION AND GENE TRANSCRIPTION. MOUSE MODELS WERE DERIVED TO STUDY THE ROLE OF THE A-TYPE LAMINS IN INTESTINES AND SKIN HOMEOSTASIS AND ONCOGENESIS. MICE LACKING LMNA IN THEIR GASTROINTESTINAL (GI) EPITHELIUM HAVE NO EFFECTS ON OVERALL GROWTH OR GI MORPHOLOGY. ON A GISPECIFIC SENSITIZED BACKGROUND, LMNA-NULL POLYP SIZE IS INCREASED. MICE WITHOUT LMNA IN THE SKIN EPIDERMIS SHOW EPIDERMAL THICKENING DUE TO HYPERPLASIA AND ABERRANT HAIR CYCLES. LOSS OF LMNA ALTERED EXPRESSION OF GENES ASSOCIATED WITH HYPERPROLIFERATION AND MALIGNANT TRANSFORMATION. THESE RESULTS INDICATE THAT A-TYPE LAMINS REGULATE CELL PROLIFERATION. USING LMNA AND LAMIN B RECEPTOR (LBR) KNOCKOUT MICE, WE SHOW ABSENCE OF BOTH PROTEINS RESULTS IN THE DISPLACEMENT OF PERIPHERAL HETEROCHROMATIN. LOSS OF LAMIN A/C RESULTS IN PROLONGED LBR EXPRESSION. THEREFORE, LAMIN A/C AND LBR HAVE IMPORTANT ROLES IN CHROMATIN ORGANIZATION AND CEL
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
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- AUDREY WANG SHIMEI