Duchenne's muscular dystrophy (mdx)
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Duchenne's muscular dystrophy (mdx) models that Sylics offers:
STXBP1 early onset encephalopathy
In humans, de novo mutations in the STXBP1 gene (alias Munc18-1) lead to early infantile epileptic encephalopathies that are characterized by infantile epilepsy, intellectual disability, and can include autistic features. The protein encoded by this gene plays a critical role in synaptic neurotransmitter release. Patients receive a diverse range of primary diagnosis, including Ohtahara Syndrome, Dravet syndrome and atypical Rett syndrome.
Stxbp1 mouse model
Heterozygous loss of function in Stxbp1+/- in mice mimics symptoms seen in humans. Sylics has published this model together with collaborators (Kovacevic 2018, Brain). Stxbp1+/- show specific changes in spontaneous behavior in PhenoTyper home cages.
Epileptic discharges in the Stxbp1 model
In freely moving Stxbp1+/- mice with telemetric EEG implants, an increased number of epileptic spike wave discharges was detected. These could partially be suppressed by an anti epileptic drug (AED levetiracetam). c-Fos immunohistochemistry showed an increased number of recently active neurons, likely related to epileptic activity.
Cognitive impairment in Stxbp1 mouse model
Subtle learning and memory deficits in Stxbp1+/- mice are detectable in the reversal learning stage of the Barnes Maze (Kovacevic 2018, Brain). More recently, reproducible deficits were detected in 2 different Stxbp1+/- mutant lines in a fear conditioning test.
Kovacevic J, Maroteaux G, Schut D, Loos M, Dubey M, Pitsch J, Remmelink E, Koopmans B, Crowley J, Cornelisse LN, Sullivan PF, Schoch S, Toonen RF, Stiedl O, Verhage M. Protein instability, haploinsufficiency, and cortical hyper-excitability underlie STXBP1 encephalopathy. Brain. 2018 May 1;141(5):1350-1374.
More information
Please reach out to us if you want to learn more about using this model for drug development projects. For more information please contact us.