PCSK9, a protease that regulates the level of LDL receptors, is a new target for lowering circulating levels of LDL. Excess PCSK9 leads to a decrease in LDL receptor levels. Which one of the following tools would you use in mice to model a potential therapy for humans with familial hypercholesterolemia?
A)RNAi targeting PCSK9 in mice
B)add an extra copy of the PCSK9 gene fused to the GFP coding sequence add an extra copy of the gene encoding PCSK9
C)a microarray comparing mRNA levels in a mouse heterozygous for a loss-of-function PCSK9 allele to the wild-type mouse
D)a SNP chip using a mouse heterozygous for a loss-of-function PCSK9 allele
UNfortunately its not b, a ruled out, so it should be c or d........
Why is (A) ruled out? That looks the best bet to me
what is the answer??
To model a potential therapy for humans with familial hypercholesterolemia, where excess PCSK9 leads to a decrease in LDL receptor levels, you would need a method that directly targets and reduces the expression or function of PCSK9 in mice.
Option A) RNAi targeting PCSK9 in mice is a suitable choice. RNA interference (RNAi) is a technique that can be used to specifically silence the expression of a particular gene. By designing and delivering small interfering RNA (siRNA) molecules that target the PCSK9 gene, you can effectively reduce the production of PCSK9 in mice.
Option B) Adding an extra copy of the PCSK9 gene fused to the GFP coding sequence does not address the issue of excess PCSK9. Instead, it would lead to increased expression of PCSK9, which would worsen the situation.
Option C) Performing a microarray comparing mRNA levels in a mouse heterozygous for a loss-of-function PCSK9 allele to the wild-type mouse is a way to study the effects of the loss-of-function allele. However, this does not directly model a potential therapy for reducing PCSK9 levels.
Option D) Using a SNP chip on a mouse heterozygous for a loss-of-function PCSK9 allele is a method to analyze single nucleotide polymorphisms (SNPs) in the PCSK9 gene. While this can provide information about genetic variation, it does not directly model a potential therapy for reducing PCSK9 levels.
In conclusion, the correct choice would be A) RNAi targeting PCSK9 in mice, as it directly targets and reduces the expression of PCSK9, which is the goal in developing a therapy for lowering LDL levels in humans with familial hypercholesterolemia.