Creative Biolabs is a leading company providing a comprehensive list of rodent models of human neurological disease, coupled with various outcome measurements for efficacy evaluation studies of novel therapeutics. We have talented experts and scientists to help with selecting appropriate models and assays as well as setting up a detailed research plan based on the specific scientific needs.
Introduction of Rett Syndrome
Rett syndrome (RTT) is a genetic neurodevelopmental disorder that causes a progressive inability to perform motor task including eye, tongue, and body movements. It occurs almost exclusively in girls. RTT patients have a normal birth and continue developing normally for ~6 months, but suffer a rapid regression thereafter. The primary cause of RTT is the mutations in the gene encoding methyl-CpG-binding protein-2 (MECP2) on chromosome X. MeCP2 binds to methyl-DNA to modulate chromatin structure and gene transcription. Shortly after the identification of Mecp2 as the disease gene, mouse models of RTT have been generated by engineering Mecp2 gene deletions.
Fig.1 MeCP2 structure and function in gene regulation and chromatin remodeling. (A) A schematic diagram of MeCP2 structure with functional domains and three AT-hook domains. (B) The function of MeCP2 in transcription repression and chromatin compaction. (Xu et al. 2013)
Mecp2-null Mice
Mecp2-null mice can be generated using the Cre-loxP technology or CRISPR/Cas9 technique. These mice are normal until 5 weeks of age, when they begin to develop the disease, leading to death between 6 and 12 weeks. The initial symptoms include nervousness, trembling, piloerection, and difficulties in respiration occasionally. Moreover, mutant brains show a substantial reduction in both weight and neuronal cell size, but no obvious structural defects or signs of neurodegeneration.
Mecp2 Truncating Mutations
Mice with a truncating mutation also exhibit symptoms similar to those found in RTT patients. These mice appear normal and exhibit normal motor function for about 6 weeks, but then develop a progressive neurological disease that includes many features of RTT: tremors, motor impairments, hypoactivity, increased anxiety-related behavior, seizures, kyphosis, and stereotypic forelimb motions.
Assessments
Creative Biolabs provides various outcome measurements for efficacy studies of potential therapeutics. Respiratory patterns can be determined by body plethysmography. Our neurobehavioral testing platform conducts a comprehensive evaluation of the motor function using tests such as the open field. Tissue and blood/plasma can be collected and analyzed. Briefly, we provide assessments including but not limited to:
Fig.2 Effect of L-Dopa and L-Dopa+Ddci (dopa-decarboxylase inhibitor) treatments on the Mecp2 null phenotype. a. body weight. b. total symptom score. (Szczesna et al. 2014)
The neurological platform of Creative Biolabs provides an extensive range of rodent neurological disease models. If you are interested, click the following links for more detailed description of each model:
With our genetically engineered mouse model platform, Creative Biolabs can work with you to design customized animal models using ES cell targeting, CRISPR/Cas9, and other techniques to meet your specific research needs. Moreover, we can provide flexible study designs and protocols to develop both short and long-term animal studies that are fully compliant with regulatory agencies.
At Creative Biolabs, you will find the most comprehensive preclinical services at the most competitive prices. We are happy to share our expertise and state-of-the-art facility to boost the impact of your brilliant studies and move along your drug to clinical phases. Contact us today to discuss your project needs and experience the value of our expert service.
References
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