Behavioral and neurochemical alterations in mice lacking the RNA-binding protein translin

Joel M Stein; Wayland Bergman; Yanshan Fang; Lakesha Davison; Colleen Brensinger; Michael B Robinson; Norman B Hecht; Ted Abel

doi:10.1523/JNEUROSCI.4437-05.2006

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Behavioral and neurochemical alterations in mice lacking the RNA-binding protein translin

Journal article

Open access

Peer reviewed

Behavioral and neurochemical alterations in mice lacking the RNA-binding protein translin

Joel M Stein, Wayland Bergman, Yanshan Fang, Lakesha Davison, Colleen Brensinger, Michael B Robinson, Norman B Hecht and Ted Abel

The Journal of neuroscience, Vol.26(8), pp.2184-2196

02/22/2006

DOI: 10.1523/JNEUROSCI.4437-05.2006

PMCID: PMC6674824

PMID: 16495445

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Abstract

Synapse-specific local protein synthesis is thought to be important for neurodevelopment and plasticity and involves neuronal RNA-binding proteins that regulate the transport and translation of dendritically localized transcripts. The best characterized of these RNA-binding proteins is the fragile X mental retardation protein (FMRP). Mutations affecting the expression or function of FMRP cause fragile X syndrome in humans, and targeted deletion of the gene encoding FMRP results in developmental and behavioral alterations in mice. Translin is an RNA-binding protein that regulates mRNA transport and translation in mouse male germ cells and is proposed to play a similar role in neurons. Like FMRP, translin is present in neuronal dendrites, binds dendritically localized RNA, and associates with microtubules and motor proteins. We reported previously the production of viable homozygous translin knock-out mice, which demonstrate altered expression of multiple mRNA transcripts in the brain and mild motor impairments. Here, we report that translin knock-out mice also exhibit sex-specific differences in tests of learning and memory, locomotor activity, anxiety-related behavior, and sensorimotor gating, as well as handling-induced seizures and alterations in monoamine neurotransmitter levels in several forebrain regions. Similar behavioral and neurochemical alterations have been observed in mice lacking FMRP, suggesting that both proteins may act within the same neuronal systems and signaling pathways. Our results in mice indicate that mutations in translin may contribute to fragile X-like syndromes, mental retardation, attention deficit hyperactivity disorder, epilepsy, and autism spectrum disorders in humans.

RNA-Binding Proteins - genetics

Mice, Inbred C57BL

Neurotransmitter Agents - metabolism

Behavior, Animal - physiology

Male

Avoidance Learning - physiology

Reaction Time - physiology

DNA-Binding Proteins - genetics

DNA-Binding Proteins - deficiency

Mice, Knockout

Brain - metabolism

Animals

Maze Learning

Female

Mice

Biogenic Monoamines - metabolism

RNA-Binding Proteins - metabolism

Details

Title: Subtitle: Behavioral and neurochemical alterations in mice lacking the RNA-binding protein translin
Creators: Joel M Stein - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Wayland Bergman
Yanshan Fang
Lakesha Davison
Colleen Brensinger
Michael B Robinson
Norman B Hecht
Ted Abel
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.26(8), pp.2184-2196
Publisher: United States
DOI: 10.1523/JNEUROSCI.4437-05.2006
PMID: 16495445
PMCID: PMC6674824
ISSN: 0270-6474
eISSN: 1529-2401
Grant note: R01 MH 060244 / NIMH NIH HHS HD 28832 / NICHD NIH HHS P30 HD 026979 / NICHD NIH HHS P50 MH 6404501 / NIMH NIH HHS T32 AG00256 / NIA NIH HHS
Language: English
Date published: 02/22/2006
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984065826002771

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