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Premature death of TDP ‐43 ( A 315 T ) transgenic mice due to gastrointestinal complications prior to development of full neurological symptoms of amyotrophic lateral sclerosis
Author(s) -
Esmaeili Mohammad A.,
Panahi Marzieh,
Yadav Shilpi,
Hennings Leah,
Kiaei Mahmoud
Publication year - 2013
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/iep.12006
Subject(s) - amyotrophic lateral sclerosis , frontotemporal lobar degeneration , genetically modified mouse , transgene , paralysis , biology , pathology , transactivation , medicine , ubiquitin , frontotemporal dementia , dementia , genetics , disease , surgery , gene , transcription factor
Summary Abnormal distribution, modification and aggregation of transactivation response DNA ‐binding protein 43 ( TDP ‐43) are the hallmarks of multiple neurodegenerative diseases, especially frontotemporal lobar degeneration with ubiquitin‐positive inclusions ( FTLD ‐ U ) and amyotrophic lateral sclerosis ( ALS ). Transgenic mouse lines overexpressing wild‐type or mutant TDP ‐43 exhibit ALS‐like symptom, motor abnormalities and early paralysis followed by death. Reports on lifespan and phenotypic behaviour in P rp‐ TDP ‐43 ( A 315 T ) vary, and these animals are not fully characterized. Although it has been proposed that the approximate 20% loss of motor neurons at end stage is responsible for the severe weakness and death in TDP ‐43 mice, this degree of neurologic damage appears insufficient to cause death. Hence we studied these mice to further characterize and determine the reason for the death. Our characterization of TDP ‐43 transgenic mice showed that these mice develop ALS ‐like symptoms that later become compounded by gastrointestinal ( GI ) complications that resulted in death. This is the first report of a set of pathological evidence in the GI track that is strong indicator for the cause of death of P rp‐ hTDP ‐43 ( A 315 T ) transgenic mice.