Expression of Presenilin 1 and 2 (PS1 and PS2) in Human and Murine Tissues
Mutations in genes encoding related proteins, termed presenilin 1 (PS1) and presenilin 2 (PS2), are linked to the majority of cases with early-onset familial Alzheimer's disease (FAD). To clarify potential function(s) of presenilins and relationships of presenilin expression to pathogenesis of...
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Veröffentlicht in: | The Journal of neuroscience 1996-12, Vol.16 (23), p.7513-7525 |
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creator | Lee, Michael K Slunt, Hilda H Martin, Lee J Thinakaran, Gopal Kim, Grace Gandy, Samuel E Seeger, Mary Koo, Edward Price, Donald L Sisodia, Sangram S |
description | Mutations in genes encoding related proteins, termed presenilin 1 (PS1) and presenilin 2 (PS2), are linked to the majority of cases with early-onset familial Alzheimer's disease (FAD). To clarify potential function(s) of presenilins and relationships of presenilin expression to pathogenesis of AD, we examined the expression of PS1 and PS2 mRNA and PS1 protein in human and mouse. Semi-quantitative PCR of reverse-transcribed RNA (RT-PCR) analysis revealed that PS1 and PS2 mRNA are expressed ubiquitously and at comparable levels in most human and mouse tissues, including adult brain. However, PS1 mRNA is expressed at significantly higher levels in developing brain. In situ hybridization studies of mouse embryos revealed widespread expression of PS1 mRNA with a neural expression pattern that, in part, overlaps that reported for mRNA encoding specific Notch homologs. In situ hybridization analysis in adult mouse brain revealed that PS1 and PS2 mRNAs are enriched in neurons of the hippocampal formation and entorhinal cortex. Although PS1 and PS2 mRNA are expressed most prominently in neurons, lower but significant levels of PS1 and PS2 transcripts are also detected in white matter glial cells. Moreover, cultured neurons and astrocytes express PS1 and PS2 mRNAs. Using PS1-specific antibodies in immunoblot analysis, we demonstrate that PS1 accumulates as approximately 28 kDa N-terminal and approximately 18 kDa C-terminal fragments in brain. Immunocytochemical studies of mouse brain reveal that PS1 protein accumulates in a variety of neuronal populations with enrichment in somatodendritic and neuropil compartments. |
doi_str_mv | 10.1523/jneurosci.16-23-07513.1996 |
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To clarify potential function(s) of presenilins and relationships of presenilin expression to pathogenesis of AD, we examined the expression of PS1 and PS2 mRNA and PS1 protein in human and mouse. Semi-quantitative PCR of reverse-transcribed RNA (RT-PCR) analysis revealed that PS1 and PS2 mRNA are expressed ubiquitously and at comparable levels in most human and mouse tissues, including adult brain. However, PS1 mRNA is expressed at significantly higher levels in developing brain. In situ hybridization studies of mouse embryos revealed widespread expression of PS1 mRNA with a neural expression pattern that, in part, overlaps that reported for mRNA encoding specific Notch homologs. In situ hybridization analysis in adult mouse brain revealed that PS1 and PS2 mRNAs are enriched in neurons of the hippocampal formation and entorhinal cortex. Although PS1 and PS2 mRNA are expressed most prominently in neurons, lower but significant levels of PS1 and PS2 transcripts are also detected in white matter glial cells. Moreover, cultured neurons and astrocytes express PS1 and PS2 mRNAs. Using PS1-specific antibodies in immunoblot analysis, we demonstrate that PS1 accumulates as approximately 28 kDa N-terminal and approximately 18 kDa C-terminal fragments in brain. Immunocytochemical studies of mouse brain reveal that PS1 protein accumulates in a variety of neuronal populations with enrichment in somatodendritic and neuropil compartments.</description><identifier>ISSN: 0270-6474</identifier><identifier>EISSN: 1529-2401</identifier><identifier>DOI: 10.1523/jneurosci.16-23-07513.1996</identifier><identifier>PMID: 8922407</identifier><language>eng</language><publisher>United States: Soc Neuroscience</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Amyloid beta-Protein Precursor - genetics ; Animals ; Brain - metabolism ; Cells, Cultured ; Embryo, Mammalian - metabolism ; Humans ; Immunohistochemistry ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Mice - embryology ; Neuroglia - metabolism ; Neurons - metabolism ; Peptide Hydrolases - metabolism ; Presenilin-1 ; Presenilin-2 ; RNA, Messenger - metabolism ; Tissue Distribution</subject><ispartof>The Journal of neuroscience, 1996-12, Vol.16 (23), p.7513-7525</ispartof><rights>Copyright © 1996 Society for Neuroscience 1996</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c521t-3c258ba25876b3ad6081dc5e6a517577989f9276024d161950643d2e80e8bb033</citedby><cites>FETCH-LOGICAL-c521t-3c258ba25876b3ad6081dc5e6a517577989f9276024d161950643d2e80e8bb033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579112/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579112/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8922407$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Michael K</creatorcontrib><creatorcontrib>Slunt, Hilda H</creatorcontrib><creatorcontrib>Martin, Lee J</creatorcontrib><creatorcontrib>Thinakaran, Gopal</creatorcontrib><creatorcontrib>Kim, Grace</creatorcontrib><creatorcontrib>Gandy, Samuel E</creatorcontrib><creatorcontrib>Seeger, Mary</creatorcontrib><creatorcontrib>Koo, Edward</creatorcontrib><creatorcontrib>Price, Donald L</creatorcontrib><creatorcontrib>Sisodia, Sangram S</creatorcontrib><title>Expression of Presenilin 1 and 2 (PS1 and PS2) in Human and Murine Tissues</title><title>The Journal of neuroscience</title><addtitle>J Neurosci</addtitle><description>Mutations in genes encoding related proteins, termed presenilin 1 (PS1) and presenilin 2 (PS2), are linked to the majority of cases with early-onset familial Alzheimer's disease (FAD). To clarify potential function(s) of presenilins and relationships of presenilin expression to pathogenesis of AD, we examined the expression of PS1 and PS2 mRNA and PS1 protein in human and mouse. Semi-quantitative PCR of reverse-transcribed RNA (RT-PCR) analysis revealed that PS1 and PS2 mRNA are expressed ubiquitously and at comparable levels in most human and mouse tissues, including adult brain. However, PS1 mRNA is expressed at significantly higher levels in developing brain. In situ hybridization studies of mouse embryos revealed widespread expression of PS1 mRNA with a neural expression pattern that, in part, overlaps that reported for mRNA encoding specific Notch homologs. In situ hybridization analysis in adult mouse brain revealed that PS1 and PS2 mRNAs are enriched in neurons of the hippocampal formation and entorhinal cortex. Although PS1 and PS2 mRNA are expressed most prominently in neurons, lower but significant levels of PS1 and PS2 transcripts are also detected in white matter glial cells. Moreover, cultured neurons and astrocytes express PS1 and PS2 mRNAs. Using PS1-specific antibodies in immunoblot analysis, we demonstrate that PS1 accumulates as approximately 28 kDa N-terminal and approximately 18 kDa C-terminal fragments in brain. Immunocytochemical studies of mouse brain reveal that PS1 protein accumulates in a variety of neuronal populations with enrichment in somatodendritic and neuropil compartments.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Amyloid beta-Protein Precursor - genetics</subject><subject>Animals</subject><subject>Brain - metabolism</subject><subject>Cells, Cultured</subject><subject>Embryo, Mammalian - metabolism</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice - embryology</subject><subject>Neuroglia - metabolism</subject><subject>Neurons - metabolism</subject><subject>Peptide Hydrolases - metabolism</subject><subject>Presenilin-1</subject><subject>Presenilin-2</subject><subject>RNA, Messenger - metabolism</subject><subject>Tissue Distribution</subject><issn>0270-6474</issn><issn>1529-2401</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUdtOGzEQtVARDZdPqLTqQ6EPGzz22l73AQlFKQkKJWrg2fLuOsRo15vaWdL-Dd_Cl-GQCNEXe2bOmTOjOQh9BdwHRuj5ozOdb0Np-8BTQlMsGNA-SMn3UC8yZEoyDJ9QDxOBU56J7DM6DOERYywwiAN0kEsSKaKHJsO_S29CsK1L2nkyjbFxtrYugZdn7aqEvDyfTWeQbOLpjHxPIjTqGu3eKjedt84kdzaEzoRjtD_XdTAnu_8I3f8c3g1G6eT2ajy4nKQlI7BKaUlYXuj4CF5QXXGcQ1UywzUDwYSQuZxLIjgmWQUcJMM8oxUxOTZ5UWBKj9DFVnfZFY2pSuNWXtdq6W2j_T_Vaqv-R5xdqIf2SXEmJACJAt92Ar79ExdfqcaG0tS1dqbtghI5y6QgPBJ_bIllvHfwZv4-BLDaeKGufw3vf9_OBmMFXMX8zQu18SI2f_m45nvr7vgRP93iC_uwWFtvVGh0XUc2qPV6vdXbyNFXozKUjA</recordid><startdate>19961201</startdate><enddate>19961201</enddate><creator>Lee, Michael K</creator><creator>Slunt, Hilda H</creator><creator>Martin, Lee J</creator><creator>Thinakaran, Gopal</creator><creator>Kim, Grace</creator><creator>Gandy, Samuel E</creator><creator>Seeger, Mary</creator><creator>Koo, Edward</creator><creator>Price, Donald L</creator><creator>Sisodia, Sangram S</creator><general>Soc Neuroscience</general><general>Society for Neuroscience</general><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>19961201</creationdate><title>Expression of Presenilin 1 and 2 (PS1 and PS2) in Human and Murine Tissues</title><author>Lee, Michael K ; Slunt, Hilda H ; Martin, Lee J ; Thinakaran, Gopal ; Kim, Grace ; Gandy, Samuel E ; Seeger, Mary ; Koo, Edward ; Price, Donald L ; Sisodia, Sangram S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c521t-3c258ba25876b3ad6081dc5e6a517577989f9276024d161950643d2e80e8bb033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Amyloid beta-Protein Precursor - genetics</topic><topic>Animals</topic><topic>Brain - metabolism</topic><topic>Cells, Cultured</topic><topic>Embryo, Mammalian - metabolism</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Mice - embryology</topic><topic>Neuroglia - metabolism</topic><topic>Neurons - metabolism</topic><topic>Peptide Hydrolases - metabolism</topic><topic>Presenilin-1</topic><topic>Presenilin-2</topic><topic>RNA, Messenger - metabolism</topic><topic>Tissue Distribution</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Michael K</creatorcontrib><creatorcontrib>Slunt, Hilda H</creatorcontrib><creatorcontrib>Martin, Lee J</creatorcontrib><creatorcontrib>Thinakaran, Gopal</creatorcontrib><creatorcontrib>Kim, Grace</creatorcontrib><creatorcontrib>Gandy, Samuel E</creatorcontrib><creatorcontrib>Seeger, Mary</creatorcontrib><creatorcontrib>Koo, Edward</creatorcontrib><creatorcontrib>Price, Donald L</creatorcontrib><creatorcontrib>Sisodia, Sangram S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Michael K</au><au>Slunt, Hilda H</au><au>Martin, Lee J</au><au>Thinakaran, Gopal</au><au>Kim, Grace</au><au>Gandy, Samuel E</au><au>Seeger, Mary</au><au>Koo, Edward</au><au>Price, Donald L</au><au>Sisodia, Sangram S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of Presenilin 1 and 2 (PS1 and PS2) in Human and Murine Tissues</atitle><jtitle>The Journal of neuroscience</jtitle><addtitle>J Neurosci</addtitle><date>1996-12-01</date><risdate>1996</risdate><volume>16</volume><issue>23</issue><spage>7513</spage><epage>7525</epage><pages>7513-7525</pages><issn>0270-6474</issn><eissn>1529-2401</eissn><abstract>Mutations in genes encoding related proteins, termed presenilin 1 (PS1) and presenilin 2 (PS2), are linked to the majority of cases with early-onset familial Alzheimer's disease (FAD). To clarify potential function(s) of presenilins and relationships of presenilin expression to pathogenesis of AD, we examined the expression of PS1 and PS2 mRNA and PS1 protein in human and mouse. Semi-quantitative PCR of reverse-transcribed RNA (RT-PCR) analysis revealed that PS1 and PS2 mRNA are expressed ubiquitously and at comparable levels in most human and mouse tissues, including adult brain. However, PS1 mRNA is expressed at significantly higher levels in developing brain. In situ hybridization studies of mouse embryos revealed widespread expression of PS1 mRNA with a neural expression pattern that, in part, overlaps that reported for mRNA encoding specific Notch homologs. In situ hybridization analysis in adult mouse brain revealed that PS1 and PS2 mRNAs are enriched in neurons of the hippocampal formation and entorhinal cortex. Although PS1 and PS2 mRNA are expressed most prominently in neurons, lower but significant levels of PS1 and PS2 transcripts are also detected in white matter glial cells. Moreover, cultured neurons and astrocytes express PS1 and PS2 mRNAs. Using PS1-specific antibodies in immunoblot analysis, we demonstrate that PS1 accumulates as approximately 28 kDa N-terminal and approximately 18 kDa C-terminal fragments in brain. Immunocytochemical studies of mouse brain reveal that PS1 protein accumulates in a variety of neuronal populations with enrichment in somatodendritic and neuropil compartments.</abstract><cop>United States</cop><pub>Soc Neuroscience</pub><pmid>8922407</pmid><doi>10.1523/jneurosci.16-23-07513.1996</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult Aged Aged, 80 and over Amyloid beta-Protein Precursor - genetics Animals Brain - metabolism Cells, Cultured Embryo, Mammalian - metabolism Humans Immunohistochemistry Membrane Proteins - genetics Membrane Proteins - metabolism Mice - embryology Neuroglia - metabolism Neurons - metabolism Peptide Hydrolases - metabolism Presenilin-1 Presenilin-2 RNA, Messenger - metabolism Tissue Distribution |
title | Expression of Presenilin 1 and 2 (PS1 and PS2) in Human and Murine Tissues |
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