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      Knockout mice reveal a role for protein tyrosine phosphatase H1 in cognition

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          Abstract

          Background

          The present study has investigated the protein tyrosine phosphatase H1 (PTPH1) expression pattern in mouse brain and its impact on CNS functions.

          Methods

          We have previously described a PTPH1-KO mouse, generated by replacing the PTP catalytic and the PDZ domain with a LacZ neomycin cassette. PTPH1 expression pattern was evaluated by LacZ staining in the brain and PTPH1-KO and WT mice (n = 10 per gender per genotype) were also behaviorally tested for CNS functions.

          Results

          In CNS, PTPH1 is expressed during development and in adulthood and mainly localized in hippocampus, thalamus, cortex and cerebellum neurons. The behavioral tests performed on the PTPH1-KO mice showed an impact on working memory in male mice and an impaired learning performance at rotarod in females.

          Conclusion

          These results demonstrate for the first time a neuronal expression of PTPH1 and its functionality at the level of cognition.

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          Most cited references76

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          The use of a plus-maze to measure anxiety in the mouse.

          R Lister (1987)
          To investigate whether an elevated plus-maze consisting of two open and two closed arms could be used as a model of anxiety in the mouse, NIH Swiss mice were tested in the apparatus immediately after a holeboard test. Factor analysis of data from undrugged animals tested in the holeboard and plus-maze yielded three orthogonal factors interpreted as assessing anxiety, directed exploration and locomotion. Anxiolytic drugs (chlordiazepoxide, sodium pentobarbital and ethanol) increased the proportion of time spent on the open arms, and anxiogenic drugs (FG 7142, caffeine and picrotoxin) reduced this measure. Amphetamine and imipramine failed to alter the indices of anxiety. The anxiolytic effect of chlordiazepoxide was reduced in mice that had previously experienced the plus-maze in an undrugged state. Testing animals in the holeboard immediately before the plus-maze test significantly elevated both the percentage of time spent on the open arms and the total number of arm entries, but did not affect the behavioral response to chlordiazepoxide. The plus-maze appears to be a useful test with which to investigate both anxiolytic and anxiogenic agents.
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            Central mechanisms of motor skill learning.

            Okihide Hikosaka, Kae Nakamura, Katsuyuki Sakai … (2002)
            Recent studies have shown that frontoparietal cortices and interconnecting regions in the basal ganglia and the cerebellum are related to motor skill learning. We propose that motor skill learning occurs independently and in different coordinates in two sets of loop circuits: cortex-basal ganglia and cortex-cerebellum. This architecture accounts for the seemingly diverse features of motor learning.
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              High-throughput engineering of the mouse genome coupled with high-resolution expression analysis.

              William T. Poueymirou, Hong-Xia Su, John W Adams … (2003)
              One of the most effective approaches for determining gene function involves engineering mice with mutations or deletions in endogenous genes of interest. Historically, this approach has been limited by the difficulty and time required to generate such mice. We describe the development of a high-throughput and largely automated process, termed VelociGene, that uses targeting vectors based on bacterial artificial chromosomes (BACs). VelociGene permits genetic alteration with nucleotide precision, is not limited by the size of desired deletions, does not depend on isogenicity or on positive-negative selection, and can precisely replace the gene of interest with a reporter that allows for high-resolution localization of target-gene expression. We describe custom genetic alterations for hundreds of genes, corresponding to about 0.5-1.0% of the entire genome. We also provide dozens of informative expression patterns involving cells in the nervous system, immune system, vasculature, skeleton, fat and other tissues.
              Article 0 comments Cited 166 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Behav Brain Funct
                Title: Behavioral and Brain Functions : BBF
                Publisher: BioMed Central
                ISSN (Electronic): 1744-9081
                Publication date Collection: 2008
                Publication date (Electronic): 12 August 2008
                Volume: 4
                Page: 36
                Affiliations
                [1 ]MerckSerono Ivrea, Colleretto G. (TO) 10010, Italy
                [2 ]University of Eastern Piedmont, Novara, Italy
                Article
                Publisher ID: 1744-9081-4-36
                DOI: 10.1186/1744-9081-4-36
                PMC ID: 2531118
                PubMed ID: 18700002
                SO-VID: a5d5f08f-7e97-4d96-b643-a5ae029686ba
                Copyright © Copyright © 2008 Patrignani et al; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 26 May 2008
                Date accepted : 12 August 2008
                Categories
                Subject: Research

                ScienceOpen disciplines: Neurology
                Data availability:
                ScienceOpen disciplines: Neurology

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