Cardiovascular diseases are now the leading cause of death worldwide, posing a significant threat to human health. In China alone, there are approximately 330 million people with cardiovascular disease and 450 million with metabolic disease. The incidence of these diseases continues to rise, presenting a major public health concern that severely affects the well-being of the population.

Research on mouse disease models plays an indispensable role in understanding the underlying mechanisms and treatment methods for metabolic and cardiovascular diseases, including hypertension, hyperlipidemia, and diabetes. Cyagen offers a platform for screening and evaluating mouse models, providing researchers with a range of metabolic-related gene-editing models such as APOE, Ldlr KO (em), Lep KO, Uox-KO (Prolonged), and hREN×hAGT. These models contribute significantly to disease research and drug development by successfully replicating the pathology of their associated area(s) of research (shown in the Table below).

Gene-Targeted Mouse Models Research Application(s)
APOE Atherosclerosis
B6-db/db High blood glucose and obesity
Ldlr KO（em） Familial hypercholesterolemia
Lep KO Type 2 diabetes and obesity
Uox KO Hyperuricemia
Uox-KO（Prolonged） Hyperuricemia
Atp7b KO Copper metabolism disorders
(Wilson's disease)
Foxj1 KO Primary ciliary dyskinesia
Usp26 KO Klinefelter syndrome
(Turner syndrome)
Fah KO Tyrosinemia type I
hREN×hAGT Chronic hypertension
Alb-Cre/LSL-hLPA Cardiovascular targets
B6-hGLP-1R Metabolic targets
B6J-hANGPTL3 Metabolic targets

 

Table 1: Gene-Targeted Mouse Models and Research Applications

Model Validation - Using Ldlr KO (em) Mice as Example

Figure 1: Body Weight Changes in Wild-Type and C001392 Ldlr KO (em) Mice. Males on top, Females on bottom

Body weight changes in wild-type (WT) and Ldlr KO mice were measured weekly under both normal chow diet (CD) and high-fat diet (HFD) conditions. The results indicated that there was a similar trend in weight changes between Ldlr KO mice and WT mice regardless of the diet type (CD or HFD), without significant difference.


Figure 2: Blood Biochemical Analysis of Wild-Type and C001392 Ldlr KO (em) Mice. Males on top, Females on bottom; CHOL: Cholesterol; TRIG: Triglycerides; HDL: High-Density Lipoprotein; LDL: Low-Density Lipoprotein.

Lipid metabolism markers were measured at 6th, 8th, 12th, and 16th weeks of following different diets. The results revealed that compared to WT mice, Ldlr KO mice exhibited a slight increase in blood lipid levels under normal chow diet (CD) conditions. However, when receiving a high-fat diet (HFD), Ldlr KO mice showed significantly elevated levels of all blood lipid markers, indicating that both male and female Ldlr KO mice can develop a hyperlipidemia phenotype under high-fat feeding conditions.


Figure 3: Detection of Atherosclerotic Plaque Formation in Wild-Type and C001392 Ldlr KO (em) Mice Aorta. G1: Male WT mice + Normal Diet; G2: Female WT mice + Normal Diet; G3: Male WT mice + High-Fat Diet; G4: Female WT mice + High-Fat Diet; G5: Male Ldlr KO mice + Normal Diet; G6: Female Ldlr KO mice + Normal Diet; G7: Male Ldlr KO mice + High-Fat Diet; G8: Female Ldlr KO mice + High-Fat Diet


The aortas were examined at 16th week of feeding after following different dietary interventions. Male Ldlr KO mice (G7) and female Ldlr KO mice (G8), both fed with HFD, exhibited pathological plaques in their aortas compared to other control mice. This indicates that a HFD successfully induced the development of atherosclerosis in Ldlr KO mice.

Figure 4: Pathological Progression of Atherosclerotic Plaques in C001392 Ldlr KO (em) Mouse Aorta


The results of observing aortic plaques at different time points showed that Ldlr KO mice fed a HFD for 20 weeks had more significant aortic plaque formation and a larger range of plaque formation compared to mice fed a HFD for 16 weeks. This trend was consistent in both male and female mice.

Conclusions

In conclusion, cardiovascular diseases are a major public health concern worldwide, with a rising incidence that severely affects the well-being of the population. Research on mouse disease models is crucial for understanding the underlying mechanisms and treatment methods for these diseases. Cyagen offers a platform for screening and evaluating mouse models, providing researchers with a range of metabolic-related gene-editing models. These models contribute significantly to disease research and drug development by successfully replicating the pathology of their associated area(s) of research. For example, Ldlr KO mice fed a high-fat diet for 20 weeks had more significant aortic plaque formation compared to mice fed a high-fat diet for 16 weeks, indicating that a high-fat diet successfully induced the development of atherosclerosis in Ldlr KO mice.

 

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