1.RABL2B gene mutation in a girl with mental retardation and hyperactivity.
Li-Na ZHU ; Xin LIU ; Chun-Zhi WANG ; Yan WANG ; Xiao YANG ; Wei PENG ; Wei WANG ; Ning MA
Chinese Journal of Contemporary Pediatrics 2009;11(9):780-781
Child
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Female
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Humans
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Hyperkinesis
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genetics
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Intellectual Disability
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genetics
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Mutation
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rab GTP-Binding Proteins
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genetics
2.ubtor Mutation Causes Motor Hyperactivity by Activating mTOR Signaling in Zebrafish.
Tiantian WANG ; Mingshan ZHOU ; Quan ZHANG ; Cuizhen ZHANG ; Gang PENG
Neuroscience Bulletin 2021;37(12):1658-1670
Mechanistic target of rapamycin (mTOR) signaling governs important physiological and pathological processes key to cellular life. Loss of mTOR negative regulators and subsequent over-activation of mTOR signaling are major causes underlying epileptic encephalopathy. Our previous studies showed that UBTOR/KIAA1024/MINAR1 acts as a negative regulator of mTOR signaling, but whether UBTOR plays a role in neurological diseases remains largely unknown. We therefore examined a zebrafish model and found that ubtor disruption caused increased spontaneous embryonic movement and neuronal activity in spinal interneurons, as well as the expected hyperactivation of mTOR signaling in early zebrafish embryos. In addition, mutant ubtor larvae showed increased sensitivity to the convulsant pentylenetetrazol, and both the motor activity and the neuronal activity were up-regulated. These phenotypic abnormalities in zebrafish embryos and larvae were rescued by treatment with the mTORC1 inhibitor rapamycin. Taken together, our findings show that ubtor regulates motor hyperactivity and epilepsy-like behaviors by elevating neuronal activity and activating mTOR signaling.
Animals
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Hyperkinesis/genetics*
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Mutation/genetics*
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Signal Transduction
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TOR Serine-Threonine Kinases/metabolism*
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Zebrafish/metabolism*