@article{1a5cdfe11f494510bc270b0acd2d313f,
title = "Behavioral abnormalities and circuit defects in the basal ganglia of a mouse model of 16p11.2 deletion syndrome",
abstract = "A deletion on human chromosome 16p11.2 is associated with autism spectrum disorders. We deleted the syntenic region on mouse chromosome 7F3. MRI and high-throughput single-cell transcriptomics revealed anatomical and cellular abnormalities, particularly in cortex and striatum of juvenile mutant mice (16p11+/-). We found elevated numbers of striatal medium spiny neurons (MSNs) expressing the dopamine D2 receptor (Drd2+) and fewer dopamine-sensitive (Drd1+) neurons in deep layers of cortex. Electrophysiological recordings of Drd2+ MSN revealed synaptic defects, suggesting abnormal basal ganglia circuitry function in 16p11+/- mice. This is further supported by behavioral experiments showing hyperactivity, circling, and deficits in movement control. Strikingly, 16p11+/- mice showed a complete lack of habituation reminiscent of what is observed in some autistic individuals. Our findings unveil a fundamental role of genes affected by the 16p11.2 deletion in establishing the basal ganglia circuitry and provide insights in the pathophysiology of autism.",
author = "Thomas Portmann and Mu Yang and Rong Mao and Georgia Panagiotakos and Jacob Ellegood and Gul Dolen and Bader, {Patrick L.} and Grueter, {Brad A.} and Carleton Goold and Elaine Fisher and Katherine Clifford and Pavitra Rengarajan and David Kalikhman and Darren Loureiro and Saw, {Nay L.} and Zhou Zhengqui and Miller, {Michael A.} and Lerch, {Jason P.} and Henkelman, {R. Mark} and Mehrdad Shamloo and Malenka, {Robert C.} and Crawley, {Jacqueline N.} and Dolmetsch, {Ricardo E.}",
note = "Funding Information: We would like to thank Ulrich Elling and Josef Penninger (IMBA Vienna, Austria) for help and advice on mouse ESC targeting, Marty Bigos of the Stanford shared FACS facility for assistance with clone sorting, Renee Reijo-Pera for generously providing the Biomark Instruments, Kristin L. Sainani for advice in statistical analysis of mouse behavioral data, and Yishan Sun for validating and providing primer pairs for the single-cell gene expression analysis. This research was funded by the Simons foundation SFARI grant no. 204340 (R.E.D. and J.N.C.), Nina Jauw (R.E.D.), the Swiss National Science Foundation (nos. PBSKP3-123434 and PA00P3_134196, T.P.), the NIMH Intramural Research Program and the University of California Davis MIND Institute (M.Y., D.K., D.L., and J.N.C.), an F31 NRSA from the NIMH (no. MH090648-02, G.P.), a K99 from the NIH/NIMH (no. MH091160, R.M.), and the Institute of Neurological Disorders and Stroke P30 center core grant no. NS069375-01A1 (M.S.). ",
year = "2014",
month = may,
day = "22",
doi = "10.1016/j.celrep.2014.03.036",
language = "English (US)",
volume = "7",
pages = "1077--1092",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",
}