Description: The Preclinical Models Core (PMC) supports IDDRC users who seek new treatments for IDD by studying these disorders in 3 kinds of preclinical models: (1) Rodent models: This Core component characterizes behaviors in mouse models of genetic or acquired disabilities. Measured behaviors include learning, memory, social preference, ultrasonic vocalization, sleep and anxiety. (2) Stem cell models: This Core component assists users to create disease models by generating induced pluripotent stem cells (iPSCs) using standard reprogramming technologies or by genome editing, such as CRISPR-Cas, on established iPSC lines. These cells, some derived from humans with IDD, afford a model in which to scrutinize cellular consequences of genetic disease and to evaluate the efficacy of possible therapies. (3) Tissue culture models: This Core component supports users to generate tissue culture models in which to study the development and behavior of enriched or mixed populations of primary brain cells, including neurons, astrocytes, oligodendroglia, microglia and endothelia. These cells originate in genetically manipulated rodents or they are normal cells exposed to environmental stimuli, including drugs and toxins. The Tissue Culture Service and Stem Cell Service interact closely, since they share several in vitro methodologies and serve as a conduit to drive and help design rodent behavior testing. The PMC emphasizes training of users and their staff. Trained users can continue studies in their own laboratory or they can utilize the equipment in the PMC at reduced cost. This core interacts with others in the Center. It will exchange protocols, services and best practices with other IDDRCs in the Network. Relevance to IDDRC Mission: The PMC bridges all three domains of ?Genes, Brain, and Behavior?, the theme of the CHOP/Penn IDDRC (see Overall: Overview of Center). The Core was developed in response to a user survey (2014) that emphasized a need for an IDD-focused facility for the study of mammalian behavior and one to address the potential of current stem cell technologies, including CRISPR-Cas. Eligibility: These services are available both to approved users of the IDDRC at CHOP/UPenn and to users at other Centers in the Network.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD086984-05
Application #
9831585
Study Section
Special Emphasis Panel (ZHD1)
Project Start
Project End
Budget Start
2019-11-01
Budget End
2020-05-31
Support Year
5
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19146
Niarchou, Maria; Calkins, Monica E; Moore, Tyler M et al. (2018) Attention Deficit Hyperactivity Disorder Symptoms and Psychosis in 22q11.2 Deletion Syndrome. Schizophr Bull 44:824-833
Sun, Daqiang; Ching, Christopher R K; Lin, Amy et al. (2018) Large-scale mapping of cortical alterations in 22q11.2 deletion syndrome: Convergence with idiopathic psychosis and effects of deletion size. Mol Psychiatry :
Ugras, Scott; Daniels, Malcolm J; Fazelinia, Hossein et al. (2018) Induction of the Immunoproteasome Subunit Lmp7 Links Proteostasis and Immunity in ?-Synuclein Aggregation Disorders. EBioMedicine 31:307-319
Polyak, Erzsebet; Ostrovsky, Julian; Peng, Min et al. (2018) N-acetylcysteine and vitamin E rescue animal longevity and cellular oxidative stress in pre-clinical models of mitochondrial complex I disease. Mol Genet Metab 123:449-462
Grissom, N M; McKee, S E; Schoch, H et al. (2018) Male-specific deficits in natural reward learning in a mouse model of neurodevelopmental disorders. Mol Psychiatry 23:544-555
He, Zhuohao; Guo, Jing L; McBride, Jennifer D et al. (2018) Amyloid-? plaques enhance Alzheimer's brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation. Nat Med 24:29-38
Estes, Annette; Munson, Jeffrey; John, Tanya St et al. (2018) Parent Support of Preschool Peer Relationships in Younger Siblings of Children with Autism Spectrum Disorder. J Autism Dev Disord 48:1122-1132
Young, Jami F; Jones, Jason D; Sbrilli, Marissa D et al. (2018) Long-Term Effects from a School-Based Trial Comparing Interpersonal Psychotherapy-Adolescent Skills Training to Group Counseling. J Clin Child Adolesc Psychol :1-9
Barca, Emanuele; Ganetzky, Rebecca D; Potluri, Prasanth et al. (2018) USMG5 Ashkenazi Jewish founder mutation impairs mitochondrial complex V dimerization and ATP synthesis. Hum Mol Genet 27:3305-3312
Pallathra, Ashley A; Calkins, Monica E; Parish-Morris, Julia et al. (2018) Defining behavioral components of social functioning in adults with autism spectrum disorder as targets for treatment. Autism Res 11:488-502

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