The main reason for proposing to set up this core facility is that there are several investigators involved in the SCOR proposal whose projects require expression analysis of specific genes as part of understanding the development of the heart and pathogenesis of mis-expressed genes in heart disease (Projects 2, 3, 4 and 5). One of the crucial factors necessary for the functional dissection of a gene is the analysis of its spatial and temporal expression pattern. Where and when a gene is expressed in a developing tissue is essential to understanding the molecular basis of heart development and vascular disease. Expression analyses are addressed definitively and easily by in situ hybridization of whole mouse embryos and sections of embryos using a gene probe of choice. By utilizing embryos from different developmental stages and a variety of embryo sections, both the temporal and spatial expression patterns of genes of interest can be determined. The developing mouse embryo provides an ideal model in which to study gene expression. Genes responsible for developmental defects in humans almost always have a closely related homologue in mouse (1). Moreover, due to extensive conservation of primary sequence between mouse and human genes, cross species hybridizations are frequently successful. Given the difficulties with obtaining samples of human embryos, the mouse provides an ideal alternative. In addition, location of the protein product of a gene facilitates analysis where antibodies are available. Accordingly, a core facility will be established that will bank whole mouse embryos and embryo sections from a range of developmental stages and perform in situ hybridization experiments and analyses using candidate gene probes and immunohistochemistry with specific antibodies. In situ hybridization of whole and sectioned embryos is complex and time consuming and requires a variety of skills in mouse husbandry, embryo staging, microscopy and molecular biology (2). This type of study is ideally suited to being performed by a core facility and as a service to a variety of investigators with different specific goals but a common interest in developmental and/or disease gene analysis of the heart. The main aim of this core will be to facilitate the identification of genes involved in the genetic basis of conotruncal malformations. This core will provide the technical expertise and facilities to perform spatial expression studies and to assist investigators of varying specialties with the tools to understand the biology of their heart specific genes. Projects 2, 3, 4 and 5 will be in a position to utilize this core for gene expression analyses. Expression studies require a wide variety of skills to set up. Moreover, this proposed core already has most of the necessary equipment and technical expertise in place to begin providing a service since The Children's Hospital of Philadelphia has already provided Dr. Oakey with seed money to begin this core.
| Li, You; Yagi, Hisato; Onuoha, Ezenwa Obi et al. (2016) DNAH6 and Its Interactions with PCD Genes in Heterotaxy and Primary Ciliary Dyskinesia. PLoS Genet 12:e1005821 |
| John, Anitha S; Rychik, Jack; Khan, Munziba et al. (2014) 22q11.2 deletion syndrome as a risk factor for aortic root dilation in tetralogy of Fallot. Cardiol Young 24:303-10 |
| D'Alessandro, Lisa C A; Werner, Petra; Xie, Hongbo M et al. (2014) The prevalence of 16p12.1 microdeletion in patients with left-sided cardiac lesions. Congenit Heart Dis 9:83-6 |
| D'Alessandro, Lisa C A; Latney, Brande C; Paluru, Prasuna C et al. (2013) The phenotypic spectrum of ZIC3 mutations includes isolated d-transposition of the great arteries and double outlet right ventricle. Am J Med Genet A 161A:792-802 |
| Peyvandi, Shabnam; Lupo, Philip J; Garbarini, Jennifer et al. (2013) 22q11.2 deletions in patients with conotruncal defects: data from 1,610 consecutive cases. Pediatr Cardiol 34:1687-94 |
| Penton, Andrea L; Leonard, Laura D; Spinner, Nancy B (2012) Notch signaling in human development and disease. Semin Cell Dev Biol 23:450-7 |
| Bauer, Robert C; Laney, Ayanna O; Smith, Rosemarie et al. (2010) Jagged1 (JAG1) mutations in patients with tetralogy of Fallot or pulmonic stenosis. Hum Mutat 31:594-601 |
| Goldmuntz, Elizabeth; Driscoll, Deborah A; Emanuel, Beverly S et al. (2009) Evaluation of potential modifiers of the cardiac phenotype in the 22q11.2 deletion syndrome. Birth Defects Res A Clin Mol Teratol 85:125-9 |
| Tomita-Mitchell, A; Maslen, C L; Morris, C D et al. (2007) GATA4 sequence variants in patients with congenital heart disease. J Med Genet 44:779-83 |
| Loomes, Kathleen M; Russo, Pierre; Ryan, Matthew et al. (2007) Bile duct proliferation in liver-specific Jag1 conditional knockout mice: effects of gene dosage. Hepatology 45:323-30 |
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