Developmental Abnormalities and Age-Related Neurodegeneration in a Mouse Model of down Syndrome
To study the pathogenesis of central nervous system abnormalities in Down syndrome (DS), we have analyzed a new genetic model of DS, the partial trisomy 16 (Ts65Dn) mouse. Ts65Dn mice have an extra copy of the distal aspect of mouse chromosome 16, a segment homologous to human chromosome 21 that con...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1996-11, Vol.93 (23), p.13333-13338 |
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| creator | Holtzman, David M. Santucci, Daniela Kilbridge, Joshua Chua-Couzens, Jane Fontana, David J. Daniels, Scott E. Johnson, Randolph M. Chen, Karen Sun, Yuling Carlson, Elaine Alleva, Enrico Epstein, Charles J. Mobley, William C. |
| description | To study the pathogenesis of central nervous system abnormalities in Down syndrome (DS), we have analyzed a new genetic model of DS, the partial trisomy 16 (Ts65Dn) mouse. Ts65Dn mice have an extra copy of the distal aspect of mouse chromosome 16, a segment homologous to human chromosome 21 that contains much of the genetic material responsible for the DS phenotype. Ts65Dn mice show developmental delay during the postnatal period as well as abnormal behaviors in both young and adult animals that may be analogous to mental retardation. Though the Ts65Dn brain is normal on gross examination, there is age-related degeneration of septohippocampal cholinergic neurons and astrocytic hypertrophy, markers of the Alzheimer disease pathology that is present in elderly DS individuals. These findings suggest that Ts65Dn mice may be used to study certain developmental and degenerative abnormalities in the DS brain. |
| doi_str_mv | 10.1073/pnas.93.23.13333 |
| format | Article |
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Ts65Dn mice have an extra copy of the distal aspect of mouse chromosome 16, a segment homologous to human chromosome 21 that contains much of the genetic material responsible for the DS phenotype. Ts65Dn mice show developmental delay during the postnatal period as well as abnormal behaviors in both young and adult animals that may be analogous to mental retardation. Though the Ts65Dn brain is normal on gross examination, there is age-related degeneration of septohippocampal cholinergic neurons and astrocytic hypertrophy, markers of the Alzheimer disease pathology that is present in elderly DS individuals. These findings suggest that Ts65Dn mice may be used to study certain developmental and degenerative abnormalities in the DS brain.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.93.23.13333</identifier><identifier>PMID: 8917591</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Aging - physiology ; Animal models ; Animals ; Avoidance Learning ; Biological Sciences ; Brain ; Brain - growth & development ; Brain - pathology ; Central nervous system ; Cholinergics ; Chromosome Mapping ; Chromosomes ; Disease Models, Animal ; Down syndrome ; Down Syndrome - genetics ; Down Syndrome - pathology ; Down Syndrome - physiopathology ; Female ; Genes ; Genetics ; Humans ; Learning ; Male ; Maze Learning ; Mental retardation ; Messenger RNA ; Mice ; Mice, Inbred Strains ; Mice, Neurologic Mutants ; Motor Activity ; Nerve Degeneration ; Nervous system ; Neurons ; Rodents ; Stereotyped Behavior ; Trisomy ; Vocalization, Animal</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1996-11, Vol.93 (23), p.13333-13338</ispartof><rights>Copyright 1996 National Academy of Sciences</rights><rights>Copyright National Academy of Sciences Nov 12, 1996</rights><rights>Copyright © 1996, The National Academy of Sciences of the USA 1996</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c560t-a23bdf6444da92e1247640b874afc427f3e275096493a77cb366d387eae2db3</citedby><cites>FETCH-LOGICAL-c560t-a23bdf6444da92e1247640b874afc427f3e275096493a77cb366d387eae2db3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/93/23.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/40794$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/40794$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,315,728,781,785,804,886,27929,27930,53796,53798,58022,58255</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8917591$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Holtzman, David M.</creatorcontrib><creatorcontrib>Santucci, Daniela</creatorcontrib><creatorcontrib>Kilbridge, Joshua</creatorcontrib><creatorcontrib>Chua-Couzens, Jane</creatorcontrib><creatorcontrib>Fontana, David J.</creatorcontrib><creatorcontrib>Daniels, Scott E.</creatorcontrib><creatorcontrib>Johnson, Randolph M.</creatorcontrib><creatorcontrib>Chen, Karen</creatorcontrib><creatorcontrib>Sun, Yuling</creatorcontrib><creatorcontrib>Carlson, Elaine</creatorcontrib><creatorcontrib>Alleva, Enrico</creatorcontrib><creatorcontrib>Epstein, Charles J.</creatorcontrib><creatorcontrib>Mobley, William C.</creatorcontrib><title>Developmental Abnormalities and Age-Related Neurodegeneration in a Mouse Model of down Syndrome</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>To study the pathogenesis of central nervous system abnormalities in Down syndrome (DS), we have analyzed a new genetic model of DS, the partial trisomy 16 (Ts65Dn) mouse. Ts65Dn mice have an extra copy of the distal aspect of mouse chromosome 16, a segment homologous to human chromosome 21 that contains much of the genetic material responsible for the DS phenotype. Ts65Dn mice show developmental delay during the postnatal period as well as abnormal behaviors in both young and adult animals that may be analogous to mental retardation. Though the Ts65Dn brain is normal on gross examination, there is age-related degeneration of septohippocampal cholinergic neurons and astrocytic hypertrophy, markers of the Alzheimer disease pathology that is present in elderly DS individuals. 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Ts65Dn mice have an extra copy of the distal aspect of mouse chromosome 16, a segment homologous to human chromosome 21 that contains much of the genetic material responsible for the DS phenotype. Ts65Dn mice show developmental delay during the postnatal period as well as abnormal behaviors in both young and adult animals that may be analogous to mental retardation. Though the Ts65Dn brain is normal on gross examination, there is age-related degeneration of septohippocampal cholinergic neurons and astrocytic hypertrophy, markers of the Alzheimer disease pathology that is present in elderly DS individuals. These findings suggest that Ts65Dn mice may be used to study certain developmental and degenerative abnormalities in the DS brain.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>8917591</pmid><doi>10.1073/pnas.93.23.13333</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1996-11, Vol.93 (23), p.13333-13338 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_pubmed_primary_8917591 |
| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Aging - physiology Animal models Animals Avoidance Learning Biological Sciences Brain Brain - growth & development Brain - pathology Central nervous system Cholinergics Chromosome Mapping Chromosomes Disease Models, Animal Down syndrome Down Syndrome - genetics Down Syndrome - pathology Down Syndrome - physiopathology Female Genes Genetics Humans Learning Male Maze Learning Mental retardation Messenger RNA Mice Mice, Inbred Strains Mice, Neurologic Mutants Motor Activity Nerve Degeneration Nervous system Neurons Rodents Stereotyped Behavior Trisomy Vocalization, Animal |
| title | Developmental Abnormalities and Age-Related Neurodegeneration in a Mouse Model of down Syndrome |
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