Current Research: Using transposon-mediated, gene-trap mutagenesis, we have recently generated a novel, recessive mouse mutant affecting the urinary bladder, termed Bloated Bladder (Blad). Homozygous mutants die soon after birth with a grossly distended bladder which we hypothesize impairs their ability to breath. Preliminary molecular genetic analysis indicates that the Blad phenotype is caused by a loss-of-function mutation in nicotinamide 5’-mononucleotide adenyltransferase 2 (Nmnat2) on chromosome 1. This gene has been shown to localize to the Golgi complex and is predominantly expressed in the brain. The loss of Nmnat2 expression in Blad mutants suggests its activity is important in bladder functionality during development. Our hypotheses are (1) that the enlarged bladder observed in Blad mutant mice is due to a voiding failure, secondary to an innervation defect (2) the perinatal lethality is caused by the enlarged bladder physically making breathing impossible or again innervation of the diaphragm/lungs is at fault. Further characterization of the local and systemic effects of this gene deletion in this mouse model need to be determined, but experiments are underway to identify the mechanism causing the observed bladder distention. Honors/Awards: 2008-2009 Molecular Medicine and Translational Sciences Training Grant Award Publications: Gallagher CJ, Muscat JE, Hicks AN, Zheng Y, Dyer A, Chase GA, Richie JP Jr., Lazarus P. Sex-specific association of the UDP-glucuronosyltransferase 2B17 gene deletion with decreased glucuronidation of NNAL and increased risk for lung cancer. Cancer Epidemiol Biomarkers Prev. 2007 April;16(4):823-8. Conference Abstracts: Diego Lorenzetti, Amy N. Hicks, Baisong Lu, Paul Overbeek, Colin Bishop. Genetic Analysis of the Novel Mouse Bloated Bladder Mutant (Blad). The Wake Forest Institute for Regenerative Medicine Annual Retreat, Asheville, NC, April 2009. Gang Chen, Ryan Dellinger, Carla Gallagher, Dongxiao Sun, Gary Chase, Thomas Spratt, Joshua Muscat, John Richie, Amy Hicks, Philip Lazarus. UGT2B10 is a major glucuronidator of tobacco-specific nitrosamines; association of UGT2B10 haplotypes with glucuronidation phenotypes in humans. The American Association for Cancer Research Annual Meeting, Los Angeles, CA, April 2007. Gallagher CJ, Muscat JE, Hicks AN, Dyer A, Chase GA, Richie JP Jr., Lazarus P. Gender-specific association of the UGT2B17 gene deletion with decreased glucuronidation of NNAL and increased risk for lung cancer. American Association for Cancer Research: Frontiers in Cancer Prevention Meeting, Boston, MA, November 2006. Amy N. Hicks, Carla J. Gallagher, Joshua E. Muscat, Jong-in Hahm, Philip Lazarus. Haplotyping the UGT 1A Locus using Single-walled Carbon Nanotube Scanning Probes. The Penn State University Genetics Symposium, State College, PA, April 2006. Gallagher CJ, Hicks AN, Zheng Y, Dyer A, Chase GA, Muscat JE, Lazarus P. UGT2B17 gene deletion and lung cancer risk. The American Association for Cancer Research Annual Meeting, Washington, DC, April 2006. |