Cystic Fibrosis Flashcards
Describe what the 9 variants studied in the LaRusch paper have in common with one another.
R74Q, R75Q, R117H, R170H, L9675, L997F, D1152H, S1235R, D1270N
While they do not cause cystic fibrosis, they do cause inflammation and scarring of the pancreas (chronic pancreatitis)
-They secrete chloride but not bicarbonate which is important in the pancreas, sinuses, and male reproductive tract
How do the 9 variants differ from other previously studied variants with regard to CFTR structure and function?
-They secrete chloride but not bicarbonate which is important in the pancreas, sinuses, and male reproductive tract
Describe the laboratory techniques used to characterize the isolated variants?
Cell culture and plasmids
Immunoblotting
Electrophysiolgy
Structural modeling
Describe the normal functions of CFTR.
dynamically regulated anion channel; Intracellular WNK1-SPAK activation causes CFTR to change permeability from chloride preferring to bicarbonate-preferring channel; important for absorbing and secreting fluids
How do mutations in the various functions lead to variation in diseased state?
Mutations at hinge regions
Change in channel width
What does CFTR stand for?
Cystic fibrosis transmembrane conductance regulator
What does the CFTR do?
functions as a channel that regulates the transport of ions and the movement of water across the epithelial barrier
What forms the basis for the clinical manifestations of cystic fibrosis?
mutations in CFTR
What do mutations in the CFTR affect?
epithelial innate immune function in the lung
When the epithelial innate immune function is affected in the lung what results?
exaggerated and ineffective airway inflammation that fails to eradicate pulmonary pathogens
In addition to not transporting ions, the mutated CFTR does not transfer ______ to counteract neutrophil-associated oxidative stress.
antioxidants
How is CFTR regulated?
cAMP
The bacterial infection in the lung is usually caused by what two bacteria?
S. aureus
Pseudomonas aeruginosa
