hPCSK9 Models

Expressed primarily in the liver, Proprotein Convertase Subtilisin Kexin Type 9, abbreviated as PCSK9, is a secretory factor that regulates the level of LDLR expression on the cell membrane. PCSK9 binds to LDLR, directing it to lysosomes for degradation. Research on the human PCSK9 gene has found that gain-of-function mutations are associated with familial hyperlipidemia, whereas people with loss-of-function mutations have 15 to 28 percent lower LDL-C levels. These findings suggest PCSK9 is an important regulator in the cholesterol metabolism pathway; inhibiting its expression or activity can significantly lower LDL-C levels, identifying it as an effective target for the development of anti-hyperlipidemia drugs.


Strain: B6/JGpt-Pcsk9em1Cin(hPCSK9)/Gpt

Number of lab animals: 8~10 per group, 3~5 groups

Experimental perios: 8~10 weeks


Study Outline

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Figure 1. High cholesterol diets can cause hyperlipidemia in B6-hPCSK9 mice.


Data Validation

1. mRNA Levels

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Figure 2. Human hPCSK9 mRNA was detectable in the B6-hPCSK9 mice but not in wildtype mice. The endogenous mPCSK9 mRNA was not detectable in the humanized mice. Data were presented as Mean±SD, n=8.


2. hPCSK9 Protein Levels

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Figure 3. hPCSK9 protein was detectable in the liver of B6-hPCSK9 mice, but not in the liver of C57BL/6 mice (5 weeks old).


3. LDLR protein levels

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Figure 4. There were no significant differences in the liver LDLR expression between C57BL/6 and B6-hPCSK9 mice (5 weeks old).


4. Plasma LDL-C

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Figure 5. There were no significant differences found in the plasma LDL-C level between C57BL/6 and B6-hPCSK9 mice (8 weeks old).


Efficacy Data

1. Plasma LDL-C declines under Evolocumab Treatment in hPCSK9 Mice

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Figure 6. A single dose of tail vein injection of Evolocumab (20mpk) could significantly reduce the plasma LDL-C levels of Western diet fed B6-hPCSK9 mice, but no similar effect was observed in Western diet fed C57BL/6J mice. **, p<0.01; ***, p<0.001 vs B6-hPCSK9+WD by unpaired t test.


2. LDLR protein level increases under Evolocumab Treatment in hPCSK9 Mice

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Figure 7. 3 days after a single dose of tail vein injection of Evolocumab (20mpk), the expression levels of liver LDLR expression level in western-diet-fed B6-hPCSK9 mice were significantly increased.


3. Test data of drug X

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Figure 8. Test drug X (siRNA targeted hPCSK9) significantly reduced the plasma LDL-C level in B6-hPCSK9 hyperlipidemic mice. Data were presented as Mean±SD, n=5. **,P<0.01;***,P<0.001; by unpaired t test.


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