@article{11ee0f77f50740478b2287c26f70c43a,
title = "JAKMIP1, a Novel Regulator of Neuronal Translation, Modulates Synaptic Function and Autistic-like Behaviors in Mouse",
abstract = "Autism spectrum disorder (ASD) is a heritable, common neurodevelopmental disorder with diverse genetic causes. Several studies have implicated protein synthesis as one among several of its potential convergent mechanisms. We originally identified Janus kinase and microtubule-interacting protein 1 (JAKMIP1) as differentially expressed in patients with distinct syndromic forms of ASD, fragile X syndrome, and 15q duplication syndrome. Here, we provide multiple lines of evidence that JAKMIP1 is a component of polyribosomes and an RNP translational regulatory complex that includes fragile X mental retardation protein, DEAD box helicase 5, and the poly(A) binding protein cytoplasmic 1. JAKMIP1 loss dysregulates neuronal translation during synaptic development, affecting glutamatergic NMDAR signaling, and results in social deficits, stereotyped activity, abnormal postnatal vocalizations, and other autistic-like behaviors in the mouse. These findings define an important and novel role for JAKMIP1 in neural development and further highlight pathways regulating mRNA translation during synaptogenesis in the genesis of neurodevelopmental disorders.",
author = "Berg, {Jamee M.} and Changhoon Lee and Leslie Chen and Laurie Galvan and Carlos Cepeda and Chen, {Jane Y.} and Olga Pe{\~n}agarikano and Stein, {Jason L.} and Alvin Li and Asami Oguro-Ando and Miller, {Jeremy A.} and Vashisht, {Ajay A.} and Starks, {Mary E.} and Kite, {Elyse P.} and Eric Tam and Amos Gdalyahu and Al-Sharif, {Noor B.} and Burkett, {Zachary D.} and White, {Stephanie A.} and Fears, {Scott C.} and Levine, {Michael S.} and Wohlschlegel, {James A.} and Geschwind, {Daniel H.}",
note = "Funding Information: We thank Dr. Sandra Pellegrini for J1 269–286 rabbit polyclonal antibody, rabbit preimmune serum, and human JAKMIP1 expression plasmid; Dr. Joseph Dougherty for N2A BacTrap cell lines; Dr. Claudia Bagni for protocols related to IP/RT-PCR experiments; Dr. Larry Simpson for use of an Isco Fractionator; Dr. Andrew Poulos and Dr. Jesse Cushman and the UCLA behavioral testing core for help with mouse behavioral experiments; Dr. Eunjoon Kim for the anti-SHANK2 rabbit polyclonal antibody; Hongmei Dong for technical assistance with C57BL/6 mice for developmental profiling; Grace Shin for technical assistance with genotyping; Michelle Bailhe for technical assistance with protein preparation and RNA extraction; Dr. Lars Ittner for pLVU/RED plasmid ID 24178; Elizabeth Fraley for consultation regarding USV tests; and Lauren Kawaguchi for laboratory management. The vector, embryonic stem (ES) cell(s), and/or mouse strain used for this research project was generated by the trans-NIH Knock-Out Mouse Project (KOMP) and obtained from the KOMP Repository ( https://www.komp.org ). NIH grants to Velocigene at Regeneron (U01HG004085) and the CSD Consortium (U01HG004080) funded the generation of gene-targeted ES cells for 8500 genes in the KOMP Program, which are archived and distributed by the KOMP Repository at UC Davis and CHORI (U42RR024244). This work was supported by grants NIH/NIMH F31MH088083 (J.M.B.), NIH/NIMH T32MH073526 (fellow: J.M.B.; P.I.: D.H.G.), UCLA Chancellor{\textquoteright}s Award (J.M.B.), Achievement Rewards for College Scientists (J.M.B.), NIH/NIMH K99MH102357 (J.L.S.), Autism Speaks Translational Postdoctoral Fellowship (J.L.S.), NIH/NIMH R01MH070712 (S.A.W.), NIH/NIMH K08MH086786 (S.C.F.), NIH/NICHD P30HD004612 (J. de Vellis), NIH/NIGMS R01GM089778 (J.A.W.), the Jonsson Cancer Center at UCLA (J.A.W.), Autism Center of Excellence Network grant NIH/NIMH R01MH081754 and 5R01MH100027 (D.H.G.), and CART/Autism Center of Excellence NIH/NICHD P50HD055784 (S. Bookheimer). The content described is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
doi = "10.1016/j.neuron.2015.10.031",
language = "English (US)",
volume = "88",
pages = "1173--1191",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "6",
}