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- Title
Treatments in the Mouse Model of Acetylcholine Receptor (achr) Deficiency Syndrome.
- Authors
Burke, G.; Cossins, J.; Maxwell, S.; Palace, J.; Beeson, D.
- Abstract
Introduction: Present treatments for congenital myasthenia involve drugs that modify neuromuscular junction transmission. Their effects have not been studied in detail due to limited patient numbers and lack of a suitable animal model. We have developed trangenic mice that constitutively express the human AChR gamma-subunit in an AChR epsilon-subunit knockout background and show a similar phenotype to human patients with AChR deficency syndrome. Aims: To investigate clinical and pathological effects of symptomatic treatments in the mouse model of AChR deficiency syndrome. Methods: Pyridostigmine (5 mg/kg/day), 3, 4-diaminopyridine (1 mg/kg/day) or ephedrine (25 mg/kg/day) were administered to 4-week-old transgenic mice for duration of 28 days. Clinical response was determined using functional measures of muscle strength and fatigability. Endplate AChR number and morphology was compared between treated and untreated mice. Results: Pyridostigmine significantly improved performance in tests of muscle function (P=0.03 Inverted Screen Test) in the transgenic mice. This was accompanied by an increase in endplate AChR number (P=0.01) and enlargement of the neuromuscular junction. A benefit was also seen with 3, 4-diaminopyridine although apparent tolerance developed. There were no associated changes in endplate AChR number or architecture. Ephedrine failed to show any efficacy but significantly increased endplate area.
- Subjects
CHOLINERGIC receptors
- Publication
Annals of Indian Academy of Neurology, 2007, Vol 10, p26
- ISSN
0972-2327
- Publication type
Abstract