Beware of your Cre-Ation: lacZ expression impairs neuronal integrity and hippocampus-dependent memory
ABSTRACT Expression of the lacZ‐sequence is a widely used reporter‐tool to assess the transgenic and/or transfection efficacy of a target gene in mice. Once activated, lacZ is permanently expressed. However, protein accumulation is one of the hallmarks of neurodegenerative diseases. Furthermore, the...
Gespeichert in:
| Veröffentlicht in: | Hippocampus 2016-10, Vol.26 (10), p.1250-1264 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1264 |
|---|---|
| container_issue | 10 |
| container_start_page | 1250 |
| container_title | Hippocampus |
| container_volume | 26 |
| creator | Reichel, J.M. Bedenk, B.T. Gassen, N.C. Hafner, K. Bura, S.A. Almeida-Correa, S. Genewsky, A. Dedic, N. Giesert, F. Agarwal, A. Nave, K.-A. Rein, T. Czisch, M. Deussing, J.M. Wotjak, C.T. |
| description | ABSTRACT
Expression of the lacZ‐sequence is a widely used reporter‐tool to assess the transgenic and/or transfection efficacy of a target gene in mice. Once activated, lacZ is permanently expressed. However, protein accumulation is one of the hallmarks of neurodegenerative diseases. Furthermore, the protein product of the bacterial lacZ gene is ß‐galactosidase, an analog to the mammalian senescence‐associated ß‐galactosidase, a molecular marker for aging. Therefore we studied the behavioral, structural and molecular consequences of lacZ expression in distinct neuronal sub‐populations. lacZ expression in cortical glutamatergic neurons resulted in severe impairments in hippocampus‐dependent memory accompanied by marked structural alterations throughout the CNS. In contrast, GFP expression or the expression of the ChR2/YFP fusion product in the same cell populations did not result in either cognitive or structural deficits. GABAergic lacZ expression caused significantly decreased hyper‐arousal and mild cognitive deficits. Attenuated structural and behavioral consequences of lacZ expression could also be induced in adulthood, and lacZ transfection in neuronal cell cultures significantly decreased their viability. Our findings provide a strong caveat against the use of lacZ reporter mice for phenotyping studies and point to a particular sensitivity of the hippocampus formation to detrimental consequences of lacZ expression. © 2016 Wiley Periodicals, Inc. |
| doi_str_mv | 10.1002/hipo.22601 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1827911993</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1827911993</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4981-7056cab3adf7839933421cdc2c07f399e68ded46f085238ab1f91f744ec3493</originalsourceid><addsrcrecordid>eNp9kE1P3DAQhq2KqsDSS39AZYlLVSngsZ0Pc4MtX4ICaishcbG8zgQMSZzaiSD_vlkWOHDoyePRM489LyFfgO0AY3z3znV-h_OMwQeyAUwVCbBMrC3rlCUqE7BONmO8ZwwgZewTWec5MFAy3SB4gI8mIPUVHf0Q6Dxgst873-7R2tgbik9dwBinBnVNZ1yItMUh-NbU1LU93gbXj9S0JZ1-0Xlrmm6ISYkdtiW2PW2w8WHcIh8rU0f8_HLOyO-jwz_zk-T88vh0vn-eWKkKSHKWZtYshCmrvBBKCSE52NJyy_JqumNWlFjKrGJFykVhFlApqHIp0QqpxIx8W1m74P8OGHvduGixrk2LfogaCp4rgKV3RrbfoffT9tNSzxSkvJDTCzPyfUXZ4GMMWOkuuMaEUQPTy-j1Mnr9HP0Ef31RDosGyzf0NesJgBXw6Goc_6PSJ6dXl6_SZDXjYo9PbzMmPOgsF3mqry-O9c9fZ-pMXh3pH-IfyLOdxQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1821528452</pqid></control><display><type>article</type><title>Beware of your Cre-Ation: lacZ expression impairs neuronal integrity and hippocampus-dependent memory</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Reichel, J.M. ; Bedenk, B.T. ; Gassen, N.C. ; Hafner, K. ; Bura, S.A. ; Almeida-Correa, S. ; Genewsky, A. ; Dedic, N. ; Giesert, F. ; Agarwal, A. ; Nave, K.-A. ; Rein, T. ; Czisch, M. ; Deussing, J.M. ; Wotjak, C.T.</creator><creatorcontrib>Reichel, J.M. ; Bedenk, B.T. ; Gassen, N.C. ; Hafner, K. ; Bura, S.A. ; Almeida-Correa, S. ; Genewsky, A. ; Dedic, N. ; Giesert, F. ; Agarwal, A. ; Nave, K.-A. ; Rein, T. ; Czisch, M. ; Deussing, J.M. ; Wotjak, C.T.</creatorcontrib><description>ABSTRACT
Expression of the lacZ‐sequence is a widely used reporter‐tool to assess the transgenic and/or transfection efficacy of a target gene in mice. Once activated, lacZ is permanently expressed. However, protein accumulation is one of the hallmarks of neurodegenerative diseases. Furthermore, the protein product of the bacterial lacZ gene is ß‐galactosidase, an analog to the mammalian senescence‐associated ß‐galactosidase, a molecular marker for aging. Therefore we studied the behavioral, structural and molecular consequences of lacZ expression in distinct neuronal sub‐populations. lacZ expression in cortical glutamatergic neurons resulted in severe impairments in hippocampus‐dependent memory accompanied by marked structural alterations throughout the CNS. In contrast, GFP expression or the expression of the ChR2/YFP fusion product in the same cell populations did not result in either cognitive or structural deficits. GABAergic lacZ expression caused significantly decreased hyper‐arousal and mild cognitive deficits. Attenuated structural and behavioral consequences of lacZ expression could also be induced in adulthood, and lacZ transfection in neuronal cell cultures significantly decreased their viability. Our findings provide a strong caveat against the use of lacZ reporter mice for phenotyping studies and point to a particular sensitivity of the hippocampus formation to detrimental consequences of lacZ expression. © 2016 Wiley Periodicals, Inc.</description><identifier>ISSN: 1050-9631</identifier><identifier>EISSN: 1098-1063</identifier><identifier>DOI: 10.1002/hipo.22601</identifier><identifier>PMID: 27101945</identifier><identifier>CODEN: HIPPEL</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Animals ; Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; beta-Galactosidase - metabolism ; Cell Survival - physiology ; Cerebral Cortex - diagnostic imaging ; Cerebral Cortex - metabolism ; Cerebral Cortex - pathology ; cognition ; gamma-Aminobutyric Acid - metabolism ; Gene Expression ; Glutamic Acid - metabolism ; Green Fluorescent Proteins - genetics ; Green Fluorescent Proteins - metabolism ; hippocampus ; Hippocampus - diagnostic imaging ; Hippocampus - metabolism ; Hippocampus - pathology ; Integrases - genetics ; Integrases - metabolism ; Lac Operon ; Luminescent Proteins - genetics ; Luminescent Proteins - metabolism ; Memory - physiology ; memory impairment ; Mice, Inbred C57BL ; Mice, Transgenic ; neurodegeneration ; Neurons - metabolism ; Neurons - pathology ; neurotoxicity ; Recombinant Fusion Proteins - metabolism ; transgenic ; volume loss</subject><ispartof>Hippocampus, 2016-10, Vol.26 (10), p.1250-1264</ispartof><rights>2016 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4981-7056cab3adf7839933421cdc2c07f399e68ded46f085238ab1f91f744ec3493</citedby><cites>FETCH-LOGICAL-c4981-7056cab3adf7839933421cdc2c07f399e68ded46f085238ab1f91f744ec3493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fhipo.22601$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fhipo.22601$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27101945$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Reichel, J.M.</creatorcontrib><creatorcontrib>Bedenk, B.T.</creatorcontrib><creatorcontrib>Gassen, N.C.</creatorcontrib><creatorcontrib>Hafner, K.</creatorcontrib><creatorcontrib>Bura, S.A.</creatorcontrib><creatorcontrib>Almeida-Correa, S.</creatorcontrib><creatorcontrib>Genewsky, A.</creatorcontrib><creatorcontrib>Dedic, N.</creatorcontrib><creatorcontrib>Giesert, F.</creatorcontrib><creatorcontrib>Agarwal, A.</creatorcontrib><creatorcontrib>Nave, K.-A.</creatorcontrib><creatorcontrib>Rein, T.</creatorcontrib><creatorcontrib>Czisch, M.</creatorcontrib><creatorcontrib>Deussing, J.M.</creatorcontrib><creatorcontrib>Wotjak, C.T.</creatorcontrib><title>Beware of your Cre-Ation: lacZ expression impairs neuronal integrity and hippocampus-dependent memory</title><title>Hippocampus</title><addtitle>Hippocampus</addtitle><description>ABSTRACT
Expression of the lacZ‐sequence is a widely used reporter‐tool to assess the transgenic and/or transfection efficacy of a target gene in mice. Once activated, lacZ is permanently expressed. However, protein accumulation is one of the hallmarks of neurodegenerative diseases. Furthermore, the protein product of the bacterial lacZ gene is ß‐galactosidase, an analog to the mammalian senescence‐associated ß‐galactosidase, a molecular marker for aging. Therefore we studied the behavioral, structural and molecular consequences of lacZ expression in distinct neuronal sub‐populations. lacZ expression in cortical glutamatergic neurons resulted in severe impairments in hippocampus‐dependent memory accompanied by marked structural alterations throughout the CNS. In contrast, GFP expression or the expression of the ChR2/YFP fusion product in the same cell populations did not result in either cognitive or structural deficits. GABAergic lacZ expression caused significantly decreased hyper‐arousal and mild cognitive deficits. Attenuated structural and behavioral consequences of lacZ expression could also be induced in adulthood, and lacZ transfection in neuronal cell cultures significantly decreased their viability. Our findings provide a strong caveat against the use of lacZ reporter mice for phenotyping studies and point to a particular sensitivity of the hippocampus formation to detrimental consequences of lacZ expression. © 2016 Wiley Periodicals, Inc.</description><subject>Animals</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - metabolism</subject><subject>beta-Galactosidase - metabolism</subject><subject>Cell Survival - physiology</subject><subject>Cerebral Cortex - diagnostic imaging</subject><subject>Cerebral Cortex - metabolism</subject><subject>Cerebral Cortex - pathology</subject><subject>cognition</subject><subject>gamma-Aminobutyric Acid - metabolism</subject><subject>Gene Expression</subject><subject>Glutamic Acid - metabolism</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>hippocampus</subject><subject>Hippocampus - diagnostic imaging</subject><subject>Hippocampus - metabolism</subject><subject>Hippocampus - pathology</subject><subject>Integrases - genetics</subject><subject>Integrases - metabolism</subject><subject>Lac Operon</subject><subject>Luminescent Proteins - genetics</subject><subject>Luminescent Proteins - metabolism</subject><subject>Memory - physiology</subject><subject>memory impairment</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>neurodegeneration</subject><subject>Neurons - metabolism</subject><subject>Neurons - pathology</subject><subject>neurotoxicity</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>transgenic</subject><subject>volume loss</subject><issn>1050-9631</issn><issn>1098-1063</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1P3DAQhq2KqsDSS39AZYlLVSngsZ0Pc4MtX4ICaishcbG8zgQMSZzaiSD_vlkWOHDoyePRM489LyFfgO0AY3z3znV-h_OMwQeyAUwVCbBMrC3rlCUqE7BONmO8ZwwgZewTWec5MFAy3SB4gI8mIPUVHf0Q6Dxgst873-7R2tgbik9dwBinBnVNZ1yItMUh-NbU1LU93gbXj9S0JZ1-0Xlrmm6ISYkdtiW2PW2w8WHcIh8rU0f8_HLOyO-jwz_zk-T88vh0vn-eWKkKSHKWZtYshCmrvBBKCSE52NJyy_JqumNWlFjKrGJFykVhFlApqHIp0QqpxIx8W1m74P8OGHvduGixrk2LfogaCp4rgKV3RrbfoffT9tNSzxSkvJDTCzPyfUXZ4GMMWOkuuMaEUQPTy-j1Mnr9HP0Ef31RDosGyzf0NesJgBXw6Goc_6PSJ6dXl6_SZDXjYo9PbzMmPOgsF3mqry-O9c9fZ-pMXh3pH-IfyLOdxQ</recordid><startdate>201610</startdate><enddate>201610</enddate><creator>Reichel, J.M.</creator><creator>Bedenk, B.T.</creator><creator>Gassen, N.C.</creator><creator>Hafner, K.</creator><creator>Bura, S.A.</creator><creator>Almeida-Correa, S.</creator><creator>Genewsky, A.</creator><creator>Dedic, N.</creator><creator>Giesert, F.</creator><creator>Agarwal, A.</creator><creator>Nave, K.-A.</creator><creator>Rein, T.</creator><creator>Czisch, M.</creator><creator>Deussing, J.M.</creator><creator>Wotjak, C.T.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7TK</scope><scope>K9.</scope></search><sort><creationdate>201610</creationdate><title>Beware of your Cre-Ation: lacZ expression impairs neuronal integrity and hippocampus-dependent memory</title><author>Reichel, J.M. ; Bedenk, B.T. ; Gassen, N.C. ; Hafner, K. ; Bura, S.A. ; Almeida-Correa, S. ; Genewsky, A. ; Dedic, N. ; Giesert, F. ; Agarwal, A. ; Nave, K.-A. ; Rein, T. ; Czisch, M. ; Deussing, J.M. ; Wotjak, C.T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4981-7056cab3adf7839933421cdc2c07f399e68ded46f085238ab1f91f744ec3493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Bacterial Proteins - genetics</topic><topic>Bacterial Proteins - metabolism</topic><topic>beta-Galactosidase - metabolism</topic><topic>Cell Survival - physiology</topic><topic>Cerebral Cortex - diagnostic imaging</topic><topic>Cerebral Cortex - metabolism</topic><topic>Cerebral Cortex - pathology</topic><topic>cognition</topic><topic>gamma-Aminobutyric Acid - metabolism</topic><topic>Gene Expression</topic><topic>Glutamic Acid - metabolism</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Green Fluorescent Proteins - metabolism</topic><topic>hippocampus</topic><topic>Hippocampus - diagnostic imaging</topic><topic>Hippocampus - metabolism</topic><topic>Hippocampus - pathology</topic><topic>Integrases - genetics</topic><topic>Integrases - metabolism</topic><topic>Lac Operon</topic><topic>Luminescent Proteins - genetics</topic><topic>Luminescent Proteins - metabolism</topic><topic>Memory - physiology</topic><topic>memory impairment</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>neurodegeneration</topic><topic>Neurons - metabolism</topic><topic>Neurons - pathology</topic><topic>neurotoxicity</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>transgenic</topic><topic>volume loss</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reichel, J.M.</creatorcontrib><creatorcontrib>Bedenk, B.T.</creatorcontrib><creatorcontrib>Gassen, N.C.</creatorcontrib><creatorcontrib>Hafner, K.</creatorcontrib><creatorcontrib>Bura, S.A.</creatorcontrib><creatorcontrib>Almeida-Correa, S.</creatorcontrib><creatorcontrib>Genewsky, A.</creatorcontrib><creatorcontrib>Dedic, N.</creatorcontrib><creatorcontrib>Giesert, F.</creatorcontrib><creatorcontrib>Agarwal, A.</creatorcontrib><creatorcontrib>Nave, K.-A.</creatorcontrib><creatorcontrib>Rein, T.</creatorcontrib><creatorcontrib>Czisch, M.</creatorcontrib><creatorcontrib>Deussing, J.M.</creatorcontrib><creatorcontrib>Wotjak, C.T.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>Hippocampus</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Reichel, J.M.</au><au>Bedenk, B.T.</au><au>Gassen, N.C.</au><au>Hafner, K.</au><au>Bura, S.A.</au><au>Almeida-Correa, S.</au><au>Genewsky, A.</au><au>Dedic, N.</au><au>Giesert, F.</au><au>Agarwal, A.</au><au>Nave, K.-A.</au><au>Rein, T.</au><au>Czisch, M.</au><au>Deussing, J.M.</au><au>Wotjak, C.T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Beware of your Cre-Ation: lacZ expression impairs neuronal integrity and hippocampus-dependent memory</atitle><jtitle>Hippocampus</jtitle><addtitle>Hippocampus</addtitle><date>2016-10</date><risdate>2016</risdate><volume>26</volume><issue>10</issue><spage>1250</spage><epage>1264</epage><pages>1250-1264</pages><issn>1050-9631</issn><eissn>1098-1063</eissn><coden>HIPPEL</coden><abstract>ABSTRACT
Expression of the lacZ‐sequence is a widely used reporter‐tool to assess the transgenic and/or transfection efficacy of a target gene in mice. Once activated, lacZ is permanently expressed. However, protein accumulation is one of the hallmarks of neurodegenerative diseases. Furthermore, the protein product of the bacterial lacZ gene is ß‐galactosidase, an analog to the mammalian senescence‐associated ß‐galactosidase, a molecular marker for aging. Therefore we studied the behavioral, structural and molecular consequences of lacZ expression in distinct neuronal sub‐populations. lacZ expression in cortical glutamatergic neurons resulted in severe impairments in hippocampus‐dependent memory accompanied by marked structural alterations throughout the CNS. In contrast, GFP expression or the expression of the ChR2/YFP fusion product in the same cell populations did not result in either cognitive or structural deficits. GABAergic lacZ expression caused significantly decreased hyper‐arousal and mild cognitive deficits. Attenuated structural and behavioral consequences of lacZ expression could also be induced in adulthood, and lacZ transfection in neuronal cell cultures significantly decreased their viability. Our findings provide a strong caveat against the use of lacZ reporter mice for phenotyping studies and point to a particular sensitivity of the hippocampus formation to detrimental consequences of lacZ expression. © 2016 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>27101945</pmid><doi>10.1002/hipo.22601</doi><tpages>15</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1050-9631 |
| ispartof | Hippocampus, 2016-10, Vol.26 (10), p.1250-1264 |
| issn | 1050-9631 1098-1063 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1827911993 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Animals Bacterial Proteins - genetics Bacterial Proteins - metabolism beta-Galactosidase - metabolism Cell Survival - physiology Cerebral Cortex - diagnostic imaging Cerebral Cortex - metabolism Cerebral Cortex - pathology cognition gamma-Aminobutyric Acid - metabolism Gene Expression Glutamic Acid - metabolism Green Fluorescent Proteins - genetics Green Fluorescent Proteins - metabolism hippocampus Hippocampus - diagnostic imaging Hippocampus - metabolism Hippocampus - pathology Integrases - genetics Integrases - metabolism Lac Operon Luminescent Proteins - genetics Luminescent Proteins - metabolism Memory - physiology memory impairment Mice, Inbred C57BL Mice, Transgenic neurodegeneration Neurons - metabolism Neurons - pathology neurotoxicity Recombinant Fusion Proteins - metabolism transgenic volume loss |
| title | Beware of your Cre-Ation: lacZ expression impairs neuronal integrity and hippocampus-dependent memory |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T09%3A39%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Beware%20of%20your%20Cre-Ation:%20lacZ%20expression%20impairs%20neuronal%20integrity%20and%20hippocampus-dependent%20memory&rft.jtitle=Hippocampus&rft.au=Reichel,%20J.M.&rft.date=2016-10&rft.volume=26&rft.issue=10&rft.spage=1250&rft.epage=1264&rft.pages=1250-1264&rft.issn=1050-9631&rft.eissn=1098-1063&rft.coden=HIPPEL&rft_id=info:doi/10.1002/hipo.22601&rft_dat=%3Cproquest_cross%3E1827911993%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1821528452&rft_id=info:pmid/27101945&rfr_iscdi=true |