Muscle Diseases Techniques 1.1 : Functional assessments to evaluate therapeutic efficacy Flashcards
What is DMD caused by?
Complete lack of dystrophin.
Where is dystrophin found?
Around the sarcolemma.
Which parts of the body are more affected in DMD?
Lower extremity and torso more affected than upper limbs.
What is becker’s disease?
Like DMD but less severe, some dystrophin present.
What two structures does dystrophin connect?
Connects muscle fibre to the lamina, disperses forces evenly.
What kind of protein can dystrophin act like (name 2`)?
Anchoring protein and possibly signalling.
What happens to mice with dystrophin knockouts regarding lifespan?
Die prematurely.
What happens to other proteins with dystrophin absence?
Compensatory upregulation of the dstrophin like protein, utrophin.
What are mice with upregulated utrophin called?
mdx mice
What are mice with a double knockout of dystrophin and utrophin called?
dko mice.
Is the muscle an endocrine organ?
Yes.
What is the aim of treating DMD?
Improving both muscle size and functionality. Pure size increase is useless.
Are muscles from mdx mice bigger than wild type mice? How do their strengths compare?
mdx mice muscles are larger, but they have the same strength.
So overall, mdx mice muscles are weaker and fragile given no dystrophin, and lower cross sectional force.
What are some types of non/minimally invasive analysis techniques?
Running, swimming, climbing etc.
What is the vertical hang test, and is it non-invasive? Name a pro and con of this.
It is, and is the latency to fall from a hanging wire.
Cant assess specific muscles, is a crude assessment
Is simple and a natural exercise
What is the grip strength test, and is it non-invasive? Name a pro and con of this.
It is.
Mouse holds onto a bar, and lifted from its tail by the assessor.
Assesses muscle strength, and simple
Can be inaccurate as assessors hold mice differently, cant assess specific muscles
What is the difference between in vitro, in situ and in vivo?
In vitro - isolated from the body - ie cell bath
In situ - Still in the body, as real life as pissble
In vivo - assessing entire muscle group
Name an in vitro technique on muscle, a pro and con.
Muscle cut out, hooked to a force gauge.
pro - directly assesses functionality free of neurovascular influence
con-less physiological assessment
Name an in situ technique on muscle, a pro and con.
Muscles stimulated individually
pro - preserves neurovascular supply, is more physiological
con - technically difficult, menial to carry out, expensive equipment
What is a problem with individual muscle stimulation in situ?
Can be minimally invasive by anaesthetising, but cant do this too often as it might interfere.
Name a technique at the cellular level. What can it assess (name 2). Name a pro and con
Single fibres are assessed, hooked to a force gauge.
Assesses Ca2+ release and uptake
Vmax (velocity of shortening)
pro - cellular level assessment, valuable info
con - technically difficult and expensive
What happens to CK (creatine kinase) levels in damaged muscles and in DMD?
Elevated, indicating muscle trauma.
What does a drug lowering CK levels indicate?
Means its successful in lowering trauma. If CK levels remain, drug most likely isnt working.
How can dye be used to assess damage and drug vbiability?
Damaged muscles let in more dye, more damaged is more dyed.
If a drug works, muscles its affecting must be less dyed.
