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• W2772391422 abstract "Mutations or deletions of the transcription factor TCF4 are linked to Pitt-Hopkins syndrome (PTHS) and schizophrenia, suggesting that the precise pathogenic mutations dictate cellular, synaptic, and behavioral consequences. Here, we generated two novel mouse models of PTHS, one that mimics the most common pathogenic TCF4 point mutation (human R580W, mouse R579W) and one that deletes three pathogenic arginines, and explored phenotypes of these lines alongside models of pan-cellular or CNS-specific heterozygous Tcf4 disruption. We used mice of both sexes to show that impaired Tcf4 function results in consistent microcephaly, hyperactivity, reduced anxiety, and deficient spatial learning. All four PTHS mouse models demonstrated exaggerated hippocampal long-term potentiation (LTP), consistent with deficits in hippocampus-mediated behaviors. We further examined R579W mutant mice and mice with pan-cellular Tcf4 heterozygosity and found that they exhibited hippocampal NMDA receptor hyperfunction, which likely drives the enhanced LTP. Together, our data pinpoint convergent neurobiological features in PTHS mouse models and provide a foundation for preclinical studies and a rationale for testing whether NMDAR antagonists might be used to treat PTHS.SIGNIFICANCE STATEMENT Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder associated with TCF4 mutations/deletions. Despite this genetic insight, there is a need to identify the function of TCF4 in the brain. Toward this goal, we developed two mouse lines, including one harboring the most prevalent pathogenic point mutation, and compared them with two existing models that conditionally delete Tcf4 Our data identify a set of overlapping phenotypes that may serve as outcome measures for preclinical studies of PTHS treatments. We also discovered penetrant enhanced synaptic plasticity across mouse models that may be linked to increased NMDA receptor function. These data reveal convergent neurobiological characteristics of PTHS mouse models and support the further investigation of NMDA receptor antagonists as a possible PTHS treatment." @default.
• W2772391422 created "2017-12-22" @default.
• W2772391422 creator A5012104816 @default.
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• W2772391422 date "2017-12-08" @default.
• W2772391422 modified "2023-10-17" @default.
• W2772391422 title "Common Pathophysiology in Multiple Mouse Models of Pitt–Hopkins Syndrome" @default.
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• W2772391422 cites W1967841384 @default.
• W2772391422 cites W1970585366 @default.
• W2772391422 cites W1972012838 @default.
• W2772391422 cites W1972401591 @default.
• W2772391422 cites W1974485146 @default.
• W2772391422 cites W1975890560 @default.
• W2772391422 cites W1977526136 @default.
• W2772391422 cites W1978026413 @default.
• W2772391422 cites W1984359015 @default.
• W2772391422 cites W1988721955 @default.
• W2772391422 cites W2009063507 @default.
• W2772391422 cites W2009082639 @default.
• W2772391422 cites W2009942054 @default.
• W2772391422 cites W2014756302 @default.
• W2772391422 cites W2016411894 @default.
• W2772391422 cites W2016725080 @default.
• W2772391422 cites W2023148260 @default.
• W2772391422 cites W2024380057 @default.
• W2772391422 cites W2028363992 @default.
• W2772391422 cites W2031215168 @default.
• W2772391422 cites W2031356649 @default.
• W2772391422 cites W2038381750 @default.
• W2772391422 cites W2046898443 @default.
• W2772391422 cites W2047372790 @default.
• W2772391422 cites W2048393820 @default.
• W2772391422 cites W2048920034 @default.
• W2772391422 cites W2050260157 @default.
• W2772391422 cites W2056999997 @default.
• W2772391422 cites W2060430261 @default.
• W2772391422 cites W2069961692 @default.
• W2772391422 cites W2077814048 @default.
• W2772391422 cites W2089107511 @default.
• W2772391422 cites W2090004056 @default.
• W2772391422 cites W2096261947 @default.
• W2772391422 cites W2101925660 @default.
• W2772391422 cites W2106095767 @default.
• W2772391422 cites W2107844069 @default.
• W2772391422 cites W2109769177 @default.
• W2772391422 cites W2116536082 @default.
• W2772391422 cites W2124519240 @default.
• W2772391422 cites W2127205775 @default.
• W2772391422 cites W2138008971 @default.
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• W2772391422 cites W2150554943 @default.
• W2772391422 cites W2153774613 @default.
• W2772391422 cites W2155167158 @default.
• W2772391422 cites W2159031677 @default.
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• W2772391422 cites W2196375380 @default.
• W2772391422 cites W2214603529 @default.
• W2772391422 cites W2263028779 @default.
• W2772391422 cites W2286063487 @default.
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• W2772391422 doi "https://doi.org/10.1523/jneurosci.1305-17.2017" @default.
• W2772391422 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5783968" @default.
• W2772391422 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29222403" @default.
• W2772391422 hasPublicationYear "2017" @default.
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