The Ighmbp2D564N mouse model is the first SMARD1 model to demonstrate respiratory defects
| Autor: | Jose Marquez, Zayd Al Rawi, Elizabeth C. Bryda, Daniel J. Davis, Mona O. Garro-Kacher, Caley E. Smith, Christian L. Lorson, Catherine L Smith, Nicole L. Nichols, Amy N Keilholz, Jiude Mao, Eric Villalón, Sara M. Ricardez Hernandez, Toni I. Morcos, Monique A. Lorson |
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| Rok vydání: | 2021 |
| Předmět: |
Pathology
medicine.medical_specialty Sensory system Disease Biology Muscular Atrophy Spinal Mice Genetics medicine Animals Humans Respiratory system Molecular Biology Genetics (clinical) Respiratory Distress Syndrome Newborn Respiratory distress Neurodegenerative Diseases General Medicine Spinal muscular atrophy medicine.disease Phenotype Muscle atrophy DNA-Binding Proteins Disease Models Animal Muscular Atrophy Autonomic nervous system Mutation General Article medicine.symptom Transcription Factors |
| Zdroj: | Hum Mol Genet |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddab317 |
| Popis: | Spinal muscular atrophy with respiratory distress type I (SMARD1) is a neurodegenerative disease defined by respiratory distress, muscle atrophy and sensory and autonomic nervous system defects. SMARD1 is a result of mutations within the IGHMBP2 gene. We have generated six Ighmbp2 mouse models based on patient-derived mutations that result in SMARD1 and/or Charcot-Marie Tooth Type 2 (CMT2S). Here we describe the characterization of one of these models, Ighmbp2D564N (human D565N). The Ighmbp2D564N/D564N mouse model mimics important aspects of the SMARD1 disease phenotype, including motor neuron degeneration and muscle atrophy. Ighmbp2D564N/D564N is the first SMARD1 mouse model to demonstrate respiratory defects based on quantified plethysmography analyses. SMARD1 disease phenotypes, including the respiratory defects, are significantly diminished by intracerebroventricular (ICV) injection of ssAAV9-IGHMBP2 and the extent of phenotypic restoration is dose-dependent. Collectively, this model provides important biological insight into SMARD1 disease development. |
| Databáze: | OpenAIRE |
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