Download The Epidermal Expression Patterns of Selected Genes in

55093
The Epidermal Expression Patterns of Selected Genes in Dominant Negative Clim Mice
Presenter: Thu N. Pham
Mentor: Dr. Bogi Andersen
LMO4 is one of the four discovered LIM-only proteins that consists almost entirely of two cysteine-rich zinc
structures that mediates protein-protein interaction. Its expression is found in proliferating epithelial cells of
the epidermis, mammary gland, and hair follicles. Several studies have indicated LMO4 is overexpressed in
over 50% of human breast carcinomas, suggesting its role in cell growth regulation (Visvader et al 2001). A
study by Wang et al, 2004 showed the strong interaction between LMO4 and Clim2. They found LMO4
forms a complex with Clim2, which then binds to DNA binding proteins and activates transcription of target
genes. To investigate the role of the Clim2/LMO4 complex plays in epidermis, the Andersen laboratory made
a mouse expressing a dominant negative Clim co-activator under the keratin 14 promoter (K14-DN-Clim).
This dominant negative co-activator binds to the Clim2/LMO4 complex and inhibits transcription. The
effect of this disruption is progressive hair loss over the course of the mouse life. Next, we used Affymetric
microarray to profile mouse skin mRNA, and found decreased expression levels of arginase I, basonuclin and
collagen type XVII (BP180) in transgenic mice comparing to wild-type mice. We then carried out an in situ
hybridization to determine the expression patterns of these genes in wild type and transgenic mice. We found
that arginase I is expressed in the hair follicles and BP180 is expressed throughout epidermis in wild-type
mice. We did not see any signals for basonuclin. BP180 is a hemidesmosomal transmembrane protein that is
responsible for anchoring epithelial cells to the basement membrane. We believed that mutations in this gene
led to the observed blistering skin and hair loss in our K14-DN-Clim mice. In the near future, we will
determine whether the expression patterns for these genes are altered in K14-DN-Clim mice compared to
wild-type mice.