Tissue-specific expression and differential methylation at the imprinted gene Rasgrf1 in Black 6/Castaneus mice

Posted May 12th, 2010 at 1:20 pm.

Christina Harview
Mentor: Dr. Tamara Davis

Most mammalian genes are expressed biallelically; both the copy of the gene inherited from the mother, and the copy inherited from the father are expressed and functional. However, about 85 out of the approximately 25,000 genes in the human genome have been found to be expressed monoallelically. In other words, expression of imprinted genes is limited to only one parent’s copy: either the mother’s or the father’s genetic information is expressed, but not both. Although imprinted genes account for very few of the total number of genes in the body, they are extremely important for normal development as evidenced by defects in expression leading to abnormal growth patterns and higher mortality in mice.

One proposed means by which this preferential expression is controlled is called DNA methylation. During the methylation of DNA, methyl groups are added at the 5’ end of cytosines in CG pairs along the DNA strand. This differential methylation of DNA acts as a way to mark maternal and paternal genes without changing their sequence and allows the cells to regulate their expression appropriately.

My research focuses on one particular imprinted gene called the RAS protein-specific guanine nucleotide-releasing factor 1 (Rasgrf1), which affects long-term memory function and growth regulation in mice. Rasgrf1 is paternally expressed and methylated, however, its expression profile has been found to be tissue-specific. The scientific literature has reported monoallelic expression of Rasgrf1 in the brain and stomach, biallelic expression in the lung and thymus, and no expression in the liver and kidney. I will assess and analyze the expression pattern in the Black 6/Castaneus strain of hybrid mice that is currently being used in my lab. We have developed our own expression assay which has confirmed expression of Rasgrf1 in brain, stomach, lung, and thymus, but which has also detected expression in liver and kidney although the literature cites none. This discrepancy could be due to a difference in the strains of mice used for the analyses. My work will investigate whether the expression detected in liver and kidney is monoallelic or biallelic.

In addition, I will gather expression data for placenta, 8.5 dpc embryo head, and blastocysts, which has not previously been analyzed. The overall goal of my research is to determine the exact expression pattern of Rasgrf1 and compare these data with the tissue-specific methylation patterns in order to determine how they are related to expression of Rasgrf1 in various tissues.

Filed under: 2008,Davis, Dr. Tamara,Harview, Christina by Ann Dixon

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