Characterization of Pathology in Transgenic Mice Over-Expressing Human Genomic and cDNA Tau Transgenes
To examine the normal cellular function of tau and its role in pathogenesis, we have created transgenic mice that overexpress a tau transgene derived from a human PAC that contains the coding sequence, intronic regions, and regulatory regions of the human gene. All six isoforms of human tau are repr...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2000-04-01
|
| Series: | Neurobiology of Disease |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996199902796 |
| _version_ | 1818576444199010304 |
|---|---|
| author | K. Duff H. Knight L.M. Refolo S. Sanders X. Yu M. Picciano B. Malester M. Hutton J. Adamson M. Goedert K. Burki P. Davies |
| author_facet | K. Duff H. Knight L.M. Refolo S. Sanders X. Yu M. Picciano B. Malester M. Hutton J. Adamson M. Goedert K. Burki P. Davies |
| author_sort | K. Duff |
| collection | DOAJ |
| description | To examine the normal cellular function of tau and its role in pathogenesis, we have created transgenic mice that overexpress a tau transgene derived from a human PAC that contains the coding sequence, intronic regions, and regulatory regions of the human gene. All six isoforms of human tau are represented in the transgenic mouse brain at the mRNA and protein level and the human tau is distributed in neurites and at synapses, but is absent from cell bodies. A comparison between the genomic tau mice and mice that overexpress a tau cDNA transgene shows that overall, the distribution of tau is similar in the two lines, but human tau is located in the somatodendritic compartment of many neurons in the cDNA mice. Tau-immunoreactive axonal swellings were found in the spinal cords of the cDNA mice, which correlated with a hind-limb abnormality, whereas neuropathology was essentially normal in the genomic mice up to 8 months of age. |
| first_indexed | 2024-12-16T06:14:07Z |
| format | Article |
| id | doaj.art-d7daf0ec58f449bf93b99647a721122f |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-16T06:14:07Z |
| publishDate | 2000-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-d7daf0ec58f449bf93b99647a721122f2022-12-21T22:41:19ZengElsevierNeurobiology of Disease1095-953X2000-04-01728798Characterization of Pathology in Transgenic Mice Over-Expressing Human Genomic and cDNA Tau TransgenesK. Duff0H. Knight1L.M. Refolo2S. Sanders3X. Yu4M. Picciano5B. Malester6M. Hutton7J. Adamson8M. Goedert9K. Burki10P. Davies11Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, 10962; Commonwealth Biotechnologies, Inc, Richmond, Virginia, 23235; Mayo Clinic, Jacksonville, Florida, 32224; Novartis Pharmaceuticals AG, Basel, CH-4002, Switzerland; MRC Laboratory of Molecular Biology, Cambridge, CB2 2QH, United Kingdom; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, 10461Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, 10962; Commonwealth Biotechnologies, Inc, Richmond, Virginia, 23235; Mayo Clinic, Jacksonville, Florida, 32224; Novartis Pharmaceuticals AG, Basel, CH-4002, Switzerland; MRC Laboratory of Molecular Biology, Cambridge, CB2 2QH, United Kingdom; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, 10461Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, 10962; Commonwealth Biotechnologies, Inc, Richmond, Virginia, 23235; Mayo Clinic, Jacksonville, Florida, 32224; Novartis Pharmaceuticals AG, Basel, CH-4002, Switzerland; MRC Laboratory of Molecular Biology, Cambridge, CB2 2QH, United Kingdom; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, 10461Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, 10962; Commonwealth Biotechnologies, Inc, Richmond, Virginia, 23235; Mayo Clinic, Jacksonville, Florida, 32224; Novartis Pharmaceuticals AG, Basel, CH-4002, Switzerland; MRC Laboratory of Molecular Biology, Cambridge, CB2 2QH, United Kingdom; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, 10461Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, 10962; Commonwealth Biotechnologies, Inc, Richmond, Virginia, 23235; Mayo Clinic, Jacksonville, Florida, 32224; Novartis Pharmaceuticals AG, Basel, CH-4002, Switzerland; MRC Laboratory of Molecular Biology, Cambridge, CB2 2QH, United Kingdom; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, 10461Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, 10962; Commonwealth Biotechnologies, Inc, Richmond, Virginia, 23235; Mayo Clinic, Jacksonville, Florida, 32224; Novartis Pharmaceuticals AG, Basel, CH-4002, Switzerland; MRC Laboratory of Molecular Biology, Cambridge, CB2 2QH, United Kingdom; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, 10461Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, 10962; Commonwealth Biotechnologies, Inc, Richmond, Virginia, 23235; Mayo Clinic, Jacksonville, Florida, 32224; Novartis Pharmaceuticals AG, Basel, CH-4002, Switzerland; MRC Laboratory of Molecular Biology, Cambridge, CB2 2QH, United Kingdom; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, 10461Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, 10962; Commonwealth Biotechnologies, Inc, Richmond, Virginia, 23235; Mayo Clinic, Jacksonville, Florida, 32224; Novartis Pharmaceuticals AG, Basel, CH-4002, Switzerland; MRC Laboratory of Molecular Biology, Cambridge, CB2 2QH, United Kingdom; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, 10461Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, 10962; Commonwealth Biotechnologies, Inc, Richmond, Virginia, 23235; Mayo Clinic, Jacksonville, Florida, 32224; Novartis Pharmaceuticals AG, Basel, CH-4002, Switzerland; MRC Laboratory of Molecular Biology, Cambridge, CB2 2QH, United Kingdom; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, 10461Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, 10962; Commonwealth Biotechnologies, Inc, Richmond, Virginia, 23235; Mayo Clinic, Jacksonville, Florida, 32224; Novartis Pharmaceuticals AG, Basel, CH-4002, Switzerland; MRC Laboratory of Molecular Biology, Cambridge, CB2 2QH, United Kingdom; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, 10461Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, 10962; Commonwealth Biotechnologies, Inc, Richmond, Virginia, 23235; Mayo Clinic, Jacksonville, Florida, 32224; Novartis Pharmaceuticals AG, Basel, CH-4002, Switzerland; MRC Laboratory of Molecular Biology, Cambridge, CB2 2QH, United Kingdom; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, 10461Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, 10962; Commonwealth Biotechnologies, Inc, Richmond, Virginia, 23235; Mayo Clinic, Jacksonville, Florida, 32224; Novartis Pharmaceuticals AG, Basel, CH-4002, Switzerland; MRC Laboratory of Molecular Biology, Cambridge, CB2 2QH, United Kingdom; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, 10461To examine the normal cellular function of tau and its role in pathogenesis, we have created transgenic mice that overexpress a tau transgene derived from a human PAC that contains the coding sequence, intronic regions, and regulatory regions of the human gene. All six isoforms of human tau are represented in the transgenic mouse brain at the mRNA and protein level and the human tau is distributed in neurites and at synapses, but is absent from cell bodies. A comparison between the genomic tau mice and mice that overexpress a tau cDNA transgene shows that overall, the distribution of tau is similar in the two lines, but human tau is located in the somatodendritic compartment of many neurons in the cDNA mice. Tau-immunoreactive axonal swellings were found in the spinal cords of the cDNA mice, which correlated with a hind-limb abnormality, whereas neuropathology was essentially normal in the genomic mice up to 8 months of age.http://www.sciencedirect.com/science/article/pii/S0969996199902796 |
| spellingShingle | K. Duff H. Knight L.M. Refolo S. Sanders X. Yu M. Picciano B. Malester M. Hutton J. Adamson M. Goedert K. Burki P. Davies Characterization of Pathology in Transgenic Mice Over-Expressing Human Genomic and cDNA Tau Transgenes Neurobiology of Disease |
| title | Characterization of Pathology in Transgenic Mice Over-Expressing Human Genomic and cDNA Tau Transgenes |
| title_full | Characterization of Pathology in Transgenic Mice Over-Expressing Human Genomic and cDNA Tau Transgenes |
| title_fullStr | Characterization of Pathology in Transgenic Mice Over-Expressing Human Genomic and cDNA Tau Transgenes |
| title_full_unstemmed | Characterization of Pathology in Transgenic Mice Over-Expressing Human Genomic and cDNA Tau Transgenes |
| title_short | Characterization of Pathology in Transgenic Mice Over-Expressing Human Genomic and cDNA Tau Transgenes |
| title_sort | characterization of pathology in transgenic mice over expressing human genomic and cdna tau transgenes |
| url | http://www.sciencedirect.com/science/article/pii/S0969996199902796 |
| work_keys_str_mv | AT kduff characterizationofpathologyintransgenicmiceoverexpressinghumangenomicandcdnatautransgenes AT hknight characterizationofpathologyintransgenicmiceoverexpressinghumangenomicandcdnatautransgenes AT lmrefolo characterizationofpathologyintransgenicmiceoverexpressinghumangenomicandcdnatautransgenes AT ssanders characterizationofpathologyintransgenicmiceoverexpressinghumangenomicandcdnatautransgenes AT xyu characterizationofpathologyintransgenicmiceoverexpressinghumangenomicandcdnatautransgenes AT mpicciano characterizationofpathologyintransgenicmiceoverexpressinghumangenomicandcdnatautransgenes AT bmalester characterizationofpathologyintransgenicmiceoverexpressinghumangenomicandcdnatautransgenes AT mhutton characterizationofpathologyintransgenicmiceoverexpressinghumangenomicandcdnatautransgenes AT jadamson characterizationofpathologyintransgenicmiceoverexpressinghumangenomicandcdnatautransgenes AT mgoedert characterizationofpathologyintransgenicmiceoverexpressinghumangenomicandcdnatautransgenes AT kburki characterizationofpathologyintransgenicmiceoverexpressinghumangenomicandcdnatautransgenes AT pdavies characterizationofpathologyintransgenicmiceoverexpressinghumangenomicandcdnatautransgenes |