RettBASE: IRSF MECP2 Variation Database

Nucleotide sequence:

Isoform e2 cDNA Acc. N^o: NM_004992

Isoform e1 cDNA Acc. N^o: AY541280

Amino acid sequence:

Isoform e1 Protein Acc. N^o: AAS55455

Animal Models:

Guy J, Hendrich B, Holmes M, Martin JE, Bird A.
A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome.
Nat Genet 2001 Mar;27(3):322-6

Wellcome Centre for Cell Biology, Institute of Cell and Molecular Biology, University of Edinburgh, The King's Buildings, Edinburgh, UK.

"Rett syndrome (RTT) is an inherited neuro-developmental disorder of females that occurs once in 10,000-15,000 births. Affected females develop normally for 6-18 months, but then lose voluntary movements, including speech and hand skills. Most RTT patients are heterozygous for mutations in the X-linked gene MECP2 (refs. 3-12), encoding a protein that binds to methylated sites in genomic DNA and facilitates gene silencing. Previous work with Mecp2-null embryonic stem cells indicated that MeCP2 is essential for mouse embryogenesis. Here we generate mice lacking Mecp2 using Cre-loxP technology. Both Mecp2-null mice and mice in which Mecp2 was deleted in brain showed severe neurological symptoms at approximately six weeks of age. Compensation for absence of MeCP2 in other tissues by MeCP1 (refs. 19,20) was not apparent in genetic or biochemical tests. After several months, heterozygous female mice also showed behavioural symptoms. The overlapping delay before symptom onset in humans and mice, despite their profoundly different rates of development, raises the possibility that stability of brain function, not brain development per se, is compromised by the absence of MeCP2."

PMID: 11242117 [PubMed - indexed for MEDLINE]

This mouse model and others can be sourced through the Jackson Laboratories.

Chen RZ, Akbarian S, Tudor M, Jaenisch R.
Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice.
Nat Genet 2001 Mar;27(3):327-31

The Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

Mecp2 is an X-linked gene encoding a nuclear protein that binds specifically to methylated DNA (ref. 1) and functions as a general transcriptional repressor by associating with chromatin-remodelling complexes. Mecp2 is expressed at high levels in the postnatal brain, indicating that methylation-dependent regulation of gene expression may have a crucial role in the mammalian central nervous system. Consistent with this notion is the recent demonstration that MECP2 mutations cause Rett syndrome (RTT, MIM 312750), a childhood neurological disorder that represents one of the most common causes of mental retardation in females. Here we show that Mecp2-deficient mice exhibit phenotypes that resemble some of the symptoms of RTT patients. Mecp2-null mice were normal until 5 weeks of age, when they began to develop disease, leading to death between 6 and 12 weeks. Mutant brains showed substantial reduction in both weight and neuronal cell size, but no obvious structural defects or signs of neuro-degeneration. Brain-specific deletion of Mecp2 at embryonic day (E) 12 resulted in a phenotype identical to that of the null mutation, indicating that the phenotype is caused by Mecp2 deficiency in the CNS rather than in peripheral tissues. Deletion of Mecp2 in postnatal CNS neurons led to a similar neuronal phenotype, although at a later age. Our results indicate that the role of Mecp2 is not restricted to the immature brain, but becomes critical in mature neurons. Mecp2 deficiency in these neurons is sufficient to cause neuronal dysfunction with symptomatic manifestation similar to Rett syndrome.

PMID: 11242118 [PubMed - indexed for MEDLINE]

This mouse model is available from the Mutant Mouse Regional Resource Center (MMRRC) Node at the University of California, Davis (UCD).

Shahbazian M, Young J, Yuva-Paylor L, Spencer C, Antalffy B, Noebels J, Armstrong D, Paylor R, Zoghbi H.
Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3.
Neuron. 2002 Jul 18;35(2):243-54

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.

Mutations in the methyl-CpG binding protein 2 (MECP2) gene cause Rett syndrome (RTT), a neurodevelopmental disorder characterized by the loss of language and motor skills during early childhood. We generated mice with a truncating mutation similar to those found in RTT patients. These mice appeared normal and exhibited normal motor function for about 6 weeks, but then developed a progressive neurological disease that includes many features of RTT: tremors, motor impairments, hypoactivity, increased anxiety-related behavior, seizures, kyphosis, and stereotypic forelimb motions. Additionally, we show that although the truncated MeCP2 protein in these mice localizes normally to heterochromatic domains in vivo, histone H3 is hyperacetylated, providing evidence that the chromatin architecture is abnormal and that gene expression may be misregulated in this model of Rett syndrome.

PMID: 12160743 [PubMed - indexed for MEDLINE]

Mutation Nomenclature:

Den Dunnen JT, Antonarakis, SE. Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Human Mutation 2000: 15; 7 - 12.
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Or check the latest recommendations from the Human Genome Variation Society here.

HUGO Mutation Database Initiative - Relevant Publications

Other MECP2 Mutation Databases:

MeCP2.org.uk

Human Gene Mutation Database http://www.hgmd.cf.ac.uk/

"The Human Gene Mutation Database (HGMD) represents an attempt to collate known (published) gene lesions responsible for human inherited disease. This database, whilst originally established for the study of mutational mechanisms in human genes (Cooper and Krawczak 1993), has now acquired a much broader utility in that it embodies an up-to-date and comprehensive reference source to the spectrum of inherited human gene lesions. Thus, HGMD provides information of practical diagnostic importance to: (i) researchers and diagnosticians in human molecular genetics, (ii) physicians interested in a particular inherited condition in a given patient or family, and (iii) genetic counsellors."