The purpose of this core is to provide a phenotypic validation of the genetic manipulations made under the various projects. This core will provide neurobiological evaluations of trangenic and transonic lines constructed to provide overexpression of single or multiple genes from the Down syndrome region of human chromosome 21 or their murine counterparts. Behavioral, neurochemical and histological studies will be carried out to identify the specific neurobiological effects of overexpression of these genes to determine what genes singly or in combination with others may account for the mental retardation or other neurobiological outcomes exhibited in Down syndrome. The behavioral screens will include assessment of sensory and motoria development in neonatal animals, spontaneous locomotor activity in adults, and testing of aspects of learning and memory in both neonates and adults using conditioning paradigms and assessments of the animal's ability to acquire spatial discriminations and form learning sets. Brains will be screened for potential alterations in aspects of synaptic neurochemistry including assessments of norepinephrine, dopamine, serotonin and cholinergic transmission. Brains of trangenic and transonic animals will also be screened for neuropathological signs consistent with Down syndrome. These screens will include developmental and crossectional assessments of the presence of neuritic plaques, changes in synapse numbers and effects on specific synaptic membrane proteins neurofilament proteins and markers for synaptic transmitter. This Core will serve 3 of the 4 projects and provide assessments of the neurobiological outcomes of the specific manipulations proposed in those projects.
| Singh, Nandini; Dutka, Tara; Devenney, Benjamin M et al. (2015) Acute upregulation of hedgehog signaling in mice causes differential effects on cranial morphology. Dis Model Mech 8:271-9 |
| Bean, Lora J H; Allen, Emily G; Tinker, Stuart W et al. (2011) Lack of maternal folic acid supplementation is associated with heart defects in Down syndrome: a report from the National Down Syndrome Project. Birth Defects Res A Clin Mol Teratol 91:885-93 |
| Locke, Adam E; Dooley, Kenneth J; Tinker, Stuart W et al. (2010) Variation in folate pathway genes contributes to risk of congenital heart defects among individuals with Down syndrome. Genet Epidemiol 34:613-23 |
| Freeman, S B; Torfs, C P; Romitti, P A et al. (2009) Congenital gastrointestinal defects in Down syndrome: a report from the Atlanta and National Down Syndrome Projects. Clin Genet 75:180-4 |
| Lin, Yan; Tseng, George C; Cheong, Soo Yeon et al. (2008) Smarter clustering methods for SNP genotype calling. Bioinformatics 24:2665-71 |
| Freeman, Sallie B; Bean, Lora H; Allen, Emily G et al. (2008) Ethnicity, sex, and the incidence of congenital heart defects: a report from the National Down Syndrome Project. Genet Med 10:173-80 |
| Parsons, Trish; Ryan, Timothy M; Reeves, Roger H et al. (2007) Microstructure of trabecular bone in a mouse model for Down syndrome. Anat Rec (Hoboken) 290:414-21 |
| Roper, Randall J; St John, Heidi K; Philip, Jessica et al. (2006) Perinatal loss of Ts65Dn Down syndrome mice. Genetics 172:437-43 |
| Maslen, Cheryl L; Babcock, Darcie; Robinson, Susan W et al. (2006) CRELD1 mutations contribute to the occurrence of cardiac atrioventricular septal defects in Down syndrome. Am J Med Genet A 140:2501-5 |
| Richtsmeier, Joan T; Aldridge, Kristina; DeLeon, Valerie B et al. (2006) Phenotypic integration of neurocranium and brain. J Exp Zool B Mol Dev Evol 306:360-78 |
Showing the most recent 10 out of 114 publications
