A new mouse model of GLUT1 deficiency syndrome exhibits abnormal sleep-wake patterns and alterations of glucose kinetics in the brain
| Autor: | Hiroshi Mizuma, Shigeharu Wakana, Masashi Yanagisawa, Hirotaka Onoe, Hiroshi Masuya, Hiromasa Funato, Tomoko Kushida, Yuuki Hirose, Ikuo Miura, Tamio Furuse, Ikuko Yamada |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Transcription Genetic Medicine (miscellaneous) lcsh:Medicine Electroencephalography Epilepsy 0302 clinical medicine Immunology and Microbiology (miscellaneous) Missense mutation Glucose Transporter Type 1 medicine.diagnostic_test biology Behavior Animal Homozygote Brain ENU mutagenesis Embryo Loss medicine.symptom lcsh:RB1-214 Research Article Carbohydrate Metabolism Inborn Errors medicine.medical_specialty Heterozygote Ataxia Monosaccharide Transport Proteins Neuroscience (miscellaneous) Mutation Missense Motor Activity Non-rapid eye movement sleep General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Seizures Internal medicine Glucose transporter 1 medicine lcsh:Pathology Avoidance Learning Animals Learning Wakefulness GLUT1DS business.industry lcsh:R Body Weight Glucose transporter medicine.disease Mice Mutant Strains Disease Models Animal Kinetics 030104 developmental biology Endocrinology Glucose biology.protein GLUT1 business Sleep 030217 neurology & neurosurgery |
| Zdroj: | Disease Models & Mechanisms Disease Models & Mechanisms, Vol 12, Iss 9 (2019) |
| ISSN: | 1754-8411 1754-8403 |
| Popis: | Dysfunction of glucose transporter 1 (GLUT1) proteins causes infantile epilepsy, which is designated as a GLUT1 deficiency syndrome (GLUT1DS; OMIM #606777). Patients with GLUT1DS display varied clinical phenotypes, such as infantile seizures, ataxia, severe mental retardation with learning disabilities, delayed development, hypoglycorrhachia, and other varied symptoms. Glut1Rgsc200 mutant mice mutagenized with N-ethyl-N-nitrosourea (ENU) carry a missense mutation in the Glut1 gene that results in amino acid substitution at the 324th residue of the GLUT1 protein. In this study, these mutants exhibited various phenotypes, including embryonic lethality of homozygotes, a decreased cerebrospinal-fluid glucose value, deficits in contextual learning, a reduction in body size, seizure-like behavior and abnormal electroencephalogram (EEG) patterns. During EEG recording, the abnormality occurred spontaneously, whereas the seizure-like phenotypes were not observed at the same time. In sleep-wake analysis using EEG recording, heterozygotes exhibited a longer duration of wake times and shorter duration of non-rapid eye movement (NREM) sleep time. The shortened period of NREM sleep and prolonged duration of the wake period may resemble the sleep disturbances commonly observed in patients with GLUT1DS and other epilepsy disorders. Interestingly, an in vivo kinetic analysis of glucose utilization by positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose imaging revealed that glucose transportation was reduced, whereas hexokinase activity and glucose metabolism were enhanced. These results indicate that a Glut1Rgsc200 mutant is a useful tool for elucidating the molecular mechanisms of GLUT1DS. This article has an associated First Person interview with the joint first authors of the paper. Summary: New phenotypes are revealed by a GLUT1 deficiency mutant mouse model carrying a missense mutation in Glut1. |
| Databáze: | OpenAIRE |
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