Study of MeCP2 function in a mouse model of Rett syndrome

It is now commonly agreed that Rett Syndrome is a monogenic neurological disease caused by mutations in <i>MECP2 </i>gene. Rett Syndrome mainly occurs in girls and it is characterised by a period of normal development until around 6­18 months, followed by a rapid regression. After the re...

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Main Author: Kriaucinonis, S.
Published: University of Edinburgh 2005
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Online Access:http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.653565
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spelling ndltd-bl.uk-oai-ethos.bl.uk-6535652015-08-04T03:52:48ZStudy of MeCP2 function in a mouse model of Rett syndromeKriaucinonis, S.2005It is now commonly agreed that Rett Syndrome is a monogenic neurological disease caused by mutations in <i>MECP2 </i>gene. Rett Syndrome mainly occurs in girls and it is characterised by a period of normal development until around 6­18 months, followed by a rapid regression. After the regression, symptoms persist as severe mental retardation, reduced head size, seizures, ataxia, hyperventilation and repetitive hand wringing movements. The phenotype of mice with a deleted <i>Mecp2 </i>gene mimics some Rett Syndrome symptoms. The <i>Mecp2­</i>null mouse develops normally until about 6 weeks of age after which tremors, irregular breathing, lack of mobility and hindlimb clasping develop. To understand how the lack of MeCP2 causes Rett Syndrome, the search for MeCP2 regulated genes was initiated in <i>Mecp2-null </i>mouse brain. Examination of candidate genes revealed that <i>Bdnf is </i>down-regulated and <i>Hes1 is </i>up-regulated in pre, early and late symptomatic <i>Mecp2-null </i>mice. Further, global analysis of gene expression was examined by ADDER differential display. Some mis-regulated genes were identified, two of which are involved in mitochondrial respiration. Oxygen electrode measurements revealed defects in brain mitochondrial respiration, which commenced coincident with symptom onset in <i>Mecp2-null </i>mice. This finding suggests mitochondrial involvement in the pathogenesis of Rett Syndrome symptoms. In the course of these studies, the structure of the <i>Mecp2 </i>gene was re-investigated, leading to the identification of a new MeCP2 isoform. Data in this thesis demonstrates that the new isoform is the major form of MeCP2 in both mouse and human brain.572.8University of Edinburghhttp://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.653565Electronic Thesis or Dissertation
collection NDLTD
sources NDLTD
topic 572.8
spellingShingle 572.8
Kriaucinonis, S.
Study of MeCP2 function in a mouse model of Rett syndrome
description It is now commonly agreed that Rett Syndrome is a monogenic neurological disease caused by mutations in <i>MECP2 </i>gene. Rett Syndrome mainly occurs in girls and it is characterised by a period of normal development until around 6­18 months, followed by a rapid regression. After the regression, symptoms persist as severe mental retardation, reduced head size, seizures, ataxia, hyperventilation and repetitive hand wringing movements. The phenotype of mice with a deleted <i>Mecp2 </i>gene mimics some Rett Syndrome symptoms. The <i>Mecp2­</i>null mouse develops normally until about 6 weeks of age after which tremors, irregular breathing, lack of mobility and hindlimb clasping develop. To understand how the lack of MeCP2 causes Rett Syndrome, the search for MeCP2 regulated genes was initiated in <i>Mecp2-null </i>mouse brain. Examination of candidate genes revealed that <i>Bdnf is </i>down-regulated and <i>Hes1 is </i>up-regulated in pre, early and late symptomatic <i>Mecp2-null </i>mice. Further, global analysis of gene expression was examined by ADDER differential display. Some mis-regulated genes were identified, two of which are involved in mitochondrial respiration. Oxygen electrode measurements revealed defects in brain mitochondrial respiration, which commenced coincident with symptom onset in <i>Mecp2-null </i>mice. This finding suggests mitochondrial involvement in the pathogenesis of Rett Syndrome symptoms. In the course of these studies, the structure of the <i>Mecp2 </i>gene was re-investigated, leading to the identification of a new MeCP2 isoform. Data in this thesis demonstrates that the new isoform is the major form of MeCP2 in both mouse and human brain.
author Kriaucinonis, S.
author_facet Kriaucinonis, S.
author_sort Kriaucinonis, S.
title Study of MeCP2 function in a mouse model of Rett syndrome
title_short Study of MeCP2 function in a mouse model of Rett syndrome
title_full Study of MeCP2 function in a mouse model of Rett syndrome
title_fullStr Study of MeCP2 function in a mouse model of Rett syndrome
title_full_unstemmed Study of MeCP2 function in a mouse model of Rett syndrome
title_sort study of mecp2 function in a mouse model of rett syndrome
publisher University of Edinburgh
publishDate 2005
url http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.653565
work_keys_str_mv AT kriaucinoniss studyofmecp2functioninamousemodelofrettsyndrome
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