Rett syndrome
Rett syndrome is one of the most common causes of mental retardation in women, occurring in 1:10,000 to 1:15,000 female births. Affected females develop normally for the first 6 to 18 months, but subsequently lose the capacity for voluntary movements, including speech and hand skills, and many develop stereotyped, repetitive hand motions, an abnormal gait, and may suffer from seizures. Mutations in the X-linked gene methyl CpG binding protein 2 (MECP2) are responsible, and over a hundred such mutations have been identified. Drawing correlations between specific mutations and symptoms is difficult. Fewer then 1% of cases are familial. Any expectant parent is at risk for having an affected child (Rett Syndrome Research Foundation, www.rsrf.org).
JAX® Mice models
| B6.129P2(C)-Mecp2tm1.1Bird/J |
Initial efforts to generate Mecp2-null mutants were unsuccessful, presumably because the MECP2 protein is required in embryogenesis. However, Adrian Bird's group at the University of Edinburgh used Cre-lox technology to overcome the requirement. Homozygous Mecp2tm1.1Bird mice are viable and appear normal at birth. They produce no Mecp2 gene product. They develop mobility problems when 3 to 8 weeks old and exhibit hindlimb clasping and uneven breathing. About half of them develop uneven wearing of teeth because their jaws are misaligned. Although adult males have sperm in the caudal epididymis, they do not mate, and their testes remain internal. Symptoms progress variably and include weight loss, shivering, and mobility problems. They live about 50 to 60 days. Heterozygous females also develop mobility problems and hindlimb clasping, but not till they are six months old, and their symptoms do not appear to progress. Note - see the data sheet for legal and licensing information.
References
Armstrong DD. 1997. Review of Rett syndrome. J Neuropath Exp Neurol 56:843-9.
Ellaway C, Christadoulou, J. 1999. Rett syndrome: Clinical update and review of recent genetic advances. J Paediatr Child Health 35:419-26.
Guy J, Hendrich B, Holmes M, Martin JE, Bird A. 2001. A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet 27:332-6.
| B6.129S-Mecp2tm1Hzo/J |
Mice that are homozygous for the targeted mutation are viable and fertile. A truncated gene product (protein) is detected by immunohistochemical analysis of brain tissue. By 6 weeks of age, male mutant mice begin to exhibit tremors, progressive motor dysfunction, oily disheveled fur, hypoactivity, myoclonic seizures, and kyphosis. Approximately 10% of male mutants die between 10 and 12 months of age. Heterozygous female mice exhibit a milder phenotype. All mutant male mice and 62% of female heterozygotes exhibit a repetitive clasping movement of their forelimbs and exhibit tremors. The Donating Investigator reports that the myoclonic seizures, kyphosis and reduced survival were observed in aged male mutants on a 129/SvEv genetic background. Note - see the data sheet for legal and licensing information.
