Progressive Segregation of Unmyelinated Axons in Peripheral Nerves, Myelin Alterations in the CNS, and Cyst Formation in the Kidneys of Myelin and Lymphocyte Protein‐Overexpressing Mice
: Myelin and lymphocyte protein (MAL) is a putative tetraspan proteolipid that is highly expressed by Schwann cells and oligodendrocytes as a component of compact myelin. Outside of the nervous system, MAL is found in apical membranes of epithelial cells, mainly in the kidney and stomach. Because MA...
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| Veröffentlicht in: | Journal of neurochemistry 2000-11, Vol.75 (5), p.1927-1939 |
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| creator | Frank, Marcus Atanasoski, Suzana Sancho, Sara Magyar, Josef P. Rülicke, Thomas Schwab, Martin E. Suter, Ueli |
| description | : Myelin and lymphocyte protein (MAL) is a putative tetraspan proteolipid that is highly expressed by Schwann cells and oligodendrocytes as a component of compact myelin. Outside of the nervous system, MAL is found in apical membranes of epithelial cells, mainly in the kidney and stomach. Because MAL is associated with glycosphingolipids, it is thought to be involved in the organization, transport, and maintenance of glycosphingolipid‐enriched membrane microdomains. In this report, we describe the generation and analysis of transgenic mice with increased MAL gene dosage. Immunohistochemical analysis revealed that the localization of MAL overexpression in the transgenic animals corresponded closely to the MAL expression pattern observed in wildtype animals, indicating correct spatial regulation of the transgene. Phenotypically, MAL overexpression led to progressive dissociation of unmyelinated axons from bundles in the PNS, a tendency to hypomyelination and aberrant myelin formation in the CNS, and the formation of large cysts in the tubular region of the kidney. Thus, increased expression of MAL appears to be deleterious to membranous structures in the affected tissues, indicating a requirement for tight control of endogenous MAL expression in Schwann cells, oligodendrocytes, and kidney epithelial cells. |
| doi_str_mv | 10.1046/j.1471-4159.2000.0751927.x |
| format | Article |
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Outside of the nervous system, MAL is found in apical membranes of epithelial cells, mainly in the kidney and stomach. Because MAL is associated with glycosphingolipids, it is thought to be involved in the organization, transport, and maintenance of glycosphingolipid‐enriched membrane microdomains. In this report, we describe the generation and analysis of transgenic mice with increased MAL gene dosage. Immunohistochemical analysis revealed that the localization of MAL overexpression in the transgenic animals corresponded closely to the MAL expression pattern observed in wildtype animals, indicating correct spatial regulation of the transgene. Phenotypically, MAL overexpression led to progressive dissociation of unmyelinated axons from bundles in the PNS, a tendency to hypomyelination and aberrant myelin formation in the CNS, and the formation of large cysts in the tubular region of the kidney. Thus, increased expression of MAL appears to be deleterious to membranous structures in the affected tissues, indicating a requirement for tight control of endogenous MAL expression in Schwann cells, oligodendrocytes, and kidney epithelial cells.</description><identifier>ISSN: 0022-3042</identifier><identifier>EISSN: 1471-4159</identifier><identifier>DOI: 10.1046/j.1471-4159.2000.0751927.x</identifier><identifier>PMID: 11032882</identifier><identifier>CODEN: JONRA9</identifier><language>eng</language><publisher>Oxford UK: Blackwell Science Ltd</publisher><subject>Abnormalities, Multiple - genetics ; Abnormalities, Multiple - pathology ; Animals ; Atrophy ; Axons - metabolism ; Axons - pathology ; Axons - ultrastructure ; Biological and medical sciences ; Epithelial Cells - pathology ; Fundamental and applied biological sciences. Psychology ; Gastric Mucosa - metabolism ; Gastric Mucosa - pathology ; Gene Dosage ; Immunohistochemistry ; Kidney Cortex - pathology ; Kidney Tubules, Distal - pathology ; Lymphocytes - metabolism ; Membrane microdomain ; Membrane Transport Proteins ; Mice ; Mice, Transgenic ; myelin and lymphocyte protein ; Myelin and Lymphocyte-Associated Proteolipid Proteins ; Myelin Proteins ; Myelin Sheath - metabolism ; Oligodendrocyte ; Oligodendroglia - metabolism ; Oligodendroglia - pathology ; Organ Specificity - genetics ; Peripheral Nerves - metabolism ; Peripheral Nerves - pathology ; Peripheral Nerves - ultrastructure ; Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ ; Polycystic Kidney Diseases - genetics ; Polycystic Kidney Diseases - metabolism ; Polycystic Kidney Diseases - pathology ; Protein transport ; Proteolipids - genetics ; Proteolipids - metabolism ; Schwann cell ; Schwann Cells - metabolism ; Schwann Cells - pathology ; Spinal Cord - metabolism ; Spinal Cord - ultrastructure ; Vertebrates: nervous system and sense organs</subject><ispartof>Journal of neurochemistry, 2000-11, Vol.75 (5), p.1927-1939</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4027-42512d8725f021b2cbe66e7ee329d91a4aeab80ee6365c603b7f6be7b93e2c973</citedby><cites>FETCH-LOGICAL-c4027-42512d8725f021b2cbe66e7ee329d91a4aeab80ee6365c603b7f6be7b93e2c973</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1471-4159.2000.0751927.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1471-4159.2000.0751927.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,1428,27905,27906,45555,45556,46390,46814</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=839297$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11032882$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Frank, Marcus</creatorcontrib><creatorcontrib>Atanasoski, Suzana</creatorcontrib><creatorcontrib>Sancho, Sara</creatorcontrib><creatorcontrib>Magyar, Josef P.</creatorcontrib><creatorcontrib>Rülicke, Thomas</creatorcontrib><creatorcontrib>Schwab, Martin E.</creatorcontrib><creatorcontrib>Suter, Ueli</creatorcontrib><title>Progressive Segregation of Unmyelinated Axons in Peripheral Nerves, Myelin Alterations in the CNS, and Cyst Formation in the Kidneys of Myelin and Lymphocyte Protein‐Overexpressing Mice</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>: Myelin and lymphocyte protein (MAL) is a putative tetraspan proteolipid that is highly expressed by Schwann cells and oligodendrocytes as a component of compact myelin. Outside of the nervous system, MAL is found in apical membranes of epithelial cells, mainly in the kidney and stomach. Because MAL is associated with glycosphingolipids, it is thought to be involved in the organization, transport, and maintenance of glycosphingolipid‐enriched membrane microdomains. In this report, we describe the generation and analysis of transgenic mice with increased MAL gene dosage. Immunohistochemical analysis revealed that the localization of MAL overexpression in the transgenic animals corresponded closely to the MAL expression pattern observed in wildtype animals, indicating correct spatial regulation of the transgene. Phenotypically, MAL overexpression led to progressive dissociation of unmyelinated axons from bundles in the PNS, a tendency to hypomyelination and aberrant myelin formation in the CNS, and the formation of large cysts in the tubular region of the kidney. Thus, increased expression of MAL appears to be deleterious to membranous structures in the affected tissues, indicating a requirement for tight control of endogenous MAL expression in Schwann cells, oligodendrocytes, and kidney epithelial cells.</description><subject>Abnormalities, Multiple - genetics</subject><subject>Abnormalities, Multiple - pathology</subject><subject>Animals</subject><subject>Atrophy</subject><subject>Axons - metabolism</subject><subject>Axons - pathology</subject><subject>Axons - ultrastructure</subject><subject>Biological and medical sciences</subject><subject>Epithelial Cells - pathology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gastric Mucosa - metabolism</subject><subject>Gastric Mucosa - pathology</subject><subject>Gene Dosage</subject><subject>Immunohistochemistry</subject><subject>Kidney Cortex - pathology</subject><subject>Kidney Tubules, Distal - pathology</subject><subject>Lymphocytes - metabolism</subject><subject>Membrane microdomain</subject><subject>Membrane Transport Proteins</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>myelin and lymphocyte protein</subject><subject>Myelin and Lymphocyte-Associated Proteolipid Proteins</subject><subject>Myelin Proteins</subject><subject>Myelin Sheath - metabolism</subject><subject>Oligodendrocyte</subject><subject>Oligodendroglia - metabolism</subject><subject>Oligodendroglia - pathology</subject><subject>Organ Specificity - genetics</subject><subject>Peripheral Nerves - metabolism</subject><subject>Peripheral Nerves - pathology</subject><subject>Peripheral Nerves - ultrastructure</subject><subject>Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ</subject><subject>Polycystic Kidney Diseases - genetics</subject><subject>Polycystic Kidney Diseases - metabolism</subject><subject>Polycystic Kidney Diseases - pathology</subject><subject>Protein transport</subject><subject>Proteolipids - genetics</subject><subject>Proteolipids - metabolism</subject><subject>Schwann cell</subject><subject>Schwann Cells - metabolism</subject><subject>Schwann Cells - pathology</subject><subject>Spinal Cord - metabolism</subject><subject>Spinal Cord - ultrastructure</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkc1u00AUhUcIREPhFdAIJFa1mR_HY7MLFi0_aVqpdD0aj6-TieyxmXFCvOsj8D68DU-CnVhlzWp-7nfOPdJB6A0lISVR_H4b0kjQIKLzNGSEkJCIOU2ZCA9P0Oxx9BTNCGEs4CRiZ-iF91tCaBzF9Dk6o5RwliRshn7fumbtwHuzB3wHw3WtOtNY3JT43tY9VMaqDgq8ODTWY2PxLTjTbsCpCq_A7cFf4OsjhhdVN3yP6iPYbQBnq7sLrGyBs953-LJx9cl9Gn8zhYXej8smj5Fd9nW7aXTfAR7SdWDsn4dfN3twcGiPUe0aXxsNL9GzUlUeXk3nObq__PQ9-xwsb66-ZItloCPCRBCxOWVFIti8JIzmTOcQxyAAOEuLlKpIgcoTAhDzeK5jwnNRxjmIPOXAdCr4OXp38m1d82MHvpO18RqqSllodl5SIYhIIj6AH06gdo33DkrZOlMr10tK5Fid3MqxHzn2I8fq5FSdPAzi19OWXV5D8U86dTUAbydAea2q0imrjX_kEp6yY9iPJ-qnqaD_jwDy6yqbHvwvw665yg</recordid><startdate>200011</startdate><enddate>200011</enddate><creator>Frank, Marcus</creator><creator>Atanasoski, Suzana</creator><creator>Sancho, Sara</creator><creator>Magyar, Josef P.</creator><creator>Rülicke, Thomas</creator><creator>Schwab, Martin E.</creator><creator>Suter, Ueli</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><scope>IQODW</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>7TK</scope></search><sort><creationdate>200011</creationdate><title>Progressive Segregation of Unmyelinated Axons in Peripheral Nerves, Myelin Alterations in the CNS, and Cyst Formation in the Kidneys of Myelin and Lymphocyte Protein‐Overexpressing Mice</title><author>Frank, Marcus ; Atanasoski, Suzana ; Sancho, Sara ; Magyar, Josef P. ; Rülicke, Thomas ; Schwab, Martin E. ; Suter, Ueli</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4027-42512d8725f021b2cbe66e7ee329d91a4aeab80ee6365c603b7f6be7b93e2c973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Abnormalities, Multiple - genetics</topic><topic>Abnormalities, Multiple - pathology</topic><topic>Animals</topic><topic>Atrophy</topic><topic>Axons - metabolism</topic><topic>Axons - pathology</topic><topic>Axons - ultrastructure</topic><topic>Biological and medical sciences</topic><topic>Epithelial Cells - pathology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gastric Mucosa - metabolism</topic><topic>Gastric Mucosa - pathology</topic><topic>Gene Dosage</topic><topic>Immunohistochemistry</topic><topic>Kidney Cortex - pathology</topic><topic>Kidney Tubules, Distal - pathology</topic><topic>Lymphocytes - metabolism</topic><topic>Membrane microdomain</topic><topic>Membrane Transport Proteins</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>myelin and lymphocyte protein</topic><topic>Myelin and Lymphocyte-Associated Proteolipid Proteins</topic><topic>Myelin Proteins</topic><topic>Myelin Sheath - metabolism</topic><topic>Oligodendrocyte</topic><topic>Oligodendroglia - metabolism</topic><topic>Oligodendroglia - pathology</topic><topic>Organ Specificity - genetics</topic><topic>Peripheral Nerves - metabolism</topic><topic>Peripheral Nerves - pathology</topic><topic>Peripheral Nerves - ultrastructure</topic><topic>Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ</topic><topic>Polycystic Kidney Diseases - genetics</topic><topic>Polycystic Kidney Diseases - metabolism</topic><topic>Polycystic Kidney Diseases - pathology</topic><topic>Protein transport</topic><topic>Proteolipids - genetics</topic><topic>Proteolipids - metabolism</topic><topic>Schwann cell</topic><topic>Schwann Cells - metabolism</topic><topic>Schwann Cells - pathology</topic><topic>Spinal Cord - metabolism</topic><topic>Spinal Cord - ultrastructure</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Frank, Marcus</creatorcontrib><creatorcontrib>Atanasoski, Suzana</creatorcontrib><creatorcontrib>Sancho, Sara</creatorcontrib><creatorcontrib>Magyar, Josef P.</creatorcontrib><creatorcontrib>Rülicke, Thomas</creatorcontrib><creatorcontrib>Schwab, Martin E.</creatorcontrib><creatorcontrib>Suter, Ueli</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Frank, Marcus</au><au>Atanasoski, Suzana</au><au>Sancho, Sara</au><au>Magyar, Josef P.</au><au>Rülicke, Thomas</au><au>Schwab, Martin E.</au><au>Suter, Ueli</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Progressive Segregation of Unmyelinated Axons in Peripheral Nerves, Myelin Alterations in the CNS, and Cyst Formation in the Kidneys of Myelin and Lymphocyte Protein‐Overexpressing Mice</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>2000-11</date><risdate>2000</risdate><volume>75</volume><issue>5</issue><spage>1927</spage><epage>1939</epage><pages>1927-1939</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><coden>JONRA9</coden><abstract>: Myelin and lymphocyte protein (MAL) is a putative tetraspan proteolipid that is highly expressed by Schwann cells and oligodendrocytes as a component of compact myelin. Outside of the nervous system, MAL is found in apical membranes of epithelial cells, mainly in the kidney and stomach. Because MAL is associated with glycosphingolipids, it is thought to be involved in the organization, transport, and maintenance of glycosphingolipid‐enriched membrane microdomains. In this report, we describe the generation and analysis of transgenic mice with increased MAL gene dosage. Immunohistochemical analysis revealed that the localization of MAL overexpression in the transgenic animals corresponded closely to the MAL expression pattern observed in wildtype animals, indicating correct spatial regulation of the transgene. Phenotypically, MAL overexpression led to progressive dissociation of unmyelinated axons from bundles in the PNS, a tendency to hypomyelination and aberrant myelin formation in the CNS, and the formation of large cysts in the tubular region of the kidney. Thus, increased expression of MAL appears to be deleterious to membranous structures in the affected tissues, indicating a requirement for tight control of endogenous MAL expression in Schwann cells, oligodendrocytes, and kidney epithelial cells.</abstract><cop>Oxford UK</cop><pub>Blackwell Science Ltd</pub><pmid>11032882</pmid><doi>10.1046/j.1471-4159.2000.0751927.x</doi><tpages>13</tpages></addata></record> |
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| subjects | Abnormalities, Multiple - genetics Abnormalities, Multiple - pathology Animals Atrophy Axons - metabolism Axons - pathology Axons - ultrastructure Biological and medical sciences Epithelial Cells - pathology Fundamental and applied biological sciences. Psychology Gastric Mucosa - metabolism Gastric Mucosa - pathology Gene Dosage Immunohistochemistry Kidney Cortex - pathology Kidney Tubules, Distal - pathology Lymphocytes - metabolism Membrane microdomain Membrane Transport Proteins Mice Mice, Transgenic myelin and lymphocyte protein Myelin and Lymphocyte-Associated Proteolipid Proteins Myelin Proteins Myelin Sheath - metabolism Oligodendrocyte Oligodendroglia - metabolism Oligodendroglia - pathology Organ Specificity - genetics Peripheral Nerves - metabolism Peripheral Nerves - pathology Peripheral Nerves - ultrastructure Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ Polycystic Kidney Diseases - genetics Polycystic Kidney Diseases - metabolism Polycystic Kidney Diseases - pathology Protein transport Proteolipids - genetics Proteolipids - metabolism Schwann cell Schwann Cells - metabolism Schwann Cells - pathology Spinal Cord - metabolism Spinal Cord - ultrastructure Vertebrates: nervous system and sense organs |
| title | Progressive Segregation of Unmyelinated Axons in Peripheral Nerves, Myelin Alterations in the CNS, and Cyst Formation in the Kidneys of Myelin and Lymphocyte Protein‐Overexpressing Mice |
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