Limitations of human tau-expressing mouse models and novel approaches of mouse modeling for tauopathy
Neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein are primarily neuropathological features of a number of neurodegenerative diseases, collectively termed tauopathy. There is no disease-modifying drug available for tauopathy except anti-amyloid antibody therapies for Alzheime...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2023.1149761/full |
| _version_ | 1827964166774718464 |
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| author | Naruhiko Sahara Rin Yanai |
| author_facet | Naruhiko Sahara Rin Yanai |
| author_sort | Naruhiko Sahara |
| collection | DOAJ |
| description | Neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein are primarily neuropathological features of a number of neurodegenerative diseases, collectively termed tauopathy. There is no disease-modifying drug available for tauopathy except anti-amyloid antibody therapies for Alzheimer’s disease. For tau-targeting therapy, experimental models recapitulating human tau pathologies are indispensable. However, there are limited numbers of animal models that display intracellular filamentous tau aggregations. At present, several lines of P301L/S mutant tau-expressing transgenic mice successfully developed neurofibrillary pathology in the central nervous system, while most non-mutant tau-expressing transgenic mice rarely developed tau pathology. Importantly, recent studies have revealed that transgenes disrupt the coding sequence of endogenous genes, resulting in deletions and/or structural variations at the insertion site. Although any impact on the pathogenesis of tauopathy is unknown, gene disruptions may affect age-related neurodegeneration including tangle formation and brain atrophy. Moreover, some mouse lines show strain-dependent pathological features. These limitations (FTDP-17 mutations, insertion/deletion mutations, and genetic background) are a major hindrance to the establishment of a precise disease model of tauopathy. In this review, we noticed both the utility and the pitfalls of current P301L/S mutant tau-expressing transgenic mice, and we propose future strategies of mouse modeling to replicate human tauopathies. |
| first_indexed | 2024-04-09T17:11:24Z |
| format | Article |
| id | doaj.art-55b23add7f1247798482c2b41089f4b4 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-09T17:11:24Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-55b23add7f1247798482c2b41089f4b42023-04-20T05:58:11ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-04-011710.3389/fnins.2023.11497611149761Limitations of human tau-expressing mouse models and novel approaches of mouse modeling for tauopathyNaruhiko SaharaRin YanaiNeurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein are primarily neuropathological features of a number of neurodegenerative diseases, collectively termed tauopathy. There is no disease-modifying drug available for tauopathy except anti-amyloid antibody therapies for Alzheimer’s disease. For tau-targeting therapy, experimental models recapitulating human tau pathologies are indispensable. However, there are limited numbers of animal models that display intracellular filamentous tau aggregations. At present, several lines of P301L/S mutant tau-expressing transgenic mice successfully developed neurofibrillary pathology in the central nervous system, while most non-mutant tau-expressing transgenic mice rarely developed tau pathology. Importantly, recent studies have revealed that transgenes disrupt the coding sequence of endogenous genes, resulting in deletions and/or structural variations at the insertion site. Although any impact on the pathogenesis of tauopathy is unknown, gene disruptions may affect age-related neurodegeneration including tangle formation and brain atrophy. Moreover, some mouse lines show strain-dependent pathological features. These limitations (FTDP-17 mutations, insertion/deletion mutations, and genetic background) are a major hindrance to the establishment of a precise disease model of tauopathy. In this review, we noticed both the utility and the pitfalls of current P301L/S mutant tau-expressing transgenic mice, and we propose future strategies of mouse modeling to replicate human tauopathies.https://www.frontiersin.org/articles/10.3389/fnins.2023.1149761/fulltautauopathyFTDP-17 tau mutationsmouse modelneurofibrilary tangles |
| spellingShingle | Naruhiko Sahara Rin Yanai Limitations of human tau-expressing mouse models and novel approaches of mouse modeling for tauopathy Frontiers in Neuroscience tau tauopathy FTDP-17 tau mutations mouse model neurofibrilary tangles |
| title | Limitations of human tau-expressing mouse models and novel approaches of mouse modeling for tauopathy |
| title_full | Limitations of human tau-expressing mouse models and novel approaches of mouse modeling for tauopathy |
| title_fullStr | Limitations of human tau-expressing mouse models and novel approaches of mouse modeling for tauopathy |
| title_full_unstemmed | Limitations of human tau-expressing mouse models and novel approaches of mouse modeling for tauopathy |
| title_short | Limitations of human tau-expressing mouse models and novel approaches of mouse modeling for tauopathy |
| title_sort | limitations of human tau expressing mouse models and novel approaches of mouse modeling for tauopathy |
| topic | tau tauopathy FTDP-17 tau mutations mouse model neurofibrilary tangles |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2023.1149761/full |
| work_keys_str_mv | AT naruhikosahara limitationsofhumantauexpressingmousemodelsandnovelapproachesofmousemodelingfortauopathy AT rinyanai limitationsofhumantauexpressingmousemodelsandnovelapproachesofmousemodelingfortauopathy |