Question

You generate a transgenic mouse that produces 10% of the normal levels of choline acetyltransferase (ChAT) in the motor neurons. You perform physiological tests and find that the muscle contraction strength seems normal when you initially start the test. However, after repeated tests (e.g. running the mouse on a wheel), the rate of “muscle fatigue” seems to be higher in the mutant mice. Explain your observation in terms of what might be happening at the neuromuscular junction.

Answer 1

Choline acetyl transferase is an enzme found in cholinergic neurons.

It is responsible for synthesis of acetylcholine from choline and acetyl co-enzyme actyli-CoA.

Acetyl choline acs as a neurotransmitter in cholinergic nerons at the Neuro-muscular junction.

In transgenic mouse that produces 10% of the normal levels of choline acetyltransferase (ChAT) in the motor neurons leads to deceased synthesis of Acetyl choline than normal.

At rest large amount acetyl choline would have been sythesised by mutant mouse and so muscle contraction at the start of test of test seems to be normal. but on repeated tests i.e repeated stimulation leads to exhaustion of nerotransmitter Acetylcholine. Furter due decreased activity of Choline acetyl transferase productionis decreased. All this leads to exhaustion of neurotransmitter Acetylcholine, leading to muscle fatigue in mutant mouse.

Myasthenia gravis,  a disease caused due to various deficts in Nero-muscular cholinergic function. Mutations in genes ( CHAT gene) that produces Choline acetyl transferase leads to one of Congenital forms of Myasthenia Gravis