This model features targeted disruption of the endogenous LDLR (low-density lipoprotein receptor) gene in Yucatan miniature swine genetics.
In humans, loss-of-function mutations in LDLR lead to familial hypercholesterolemia, characterized by elevated plasma concentrations of cholesterol. Heterozygotes exhibit significantly higher cholesterol levels and an increased risk for atherosclerosis.
Benefits of the Model:
Consistent, stable hypercholesterolemia that can be further modulated by diet
Predictable, progressive atherosclerosis that manifests on an accelerated timeline
Atherosclerotic lesion formation in the aorta and coronary arteries that model key pathophysiological aspects of human atherosclerosis
Defined Yucatan miniature swine genetics that offers greater consistency, smaller size, and lower cost to house and manage
ExeGen® LDLR-/- Yucatan minipigs exhibit severely elevated total cholesterol levels even when fed a vegetarian, cholesterol-free diet.
Figure 1. Assessment of cholesterol levels in 26-week old ExeGen® LDLR-targeted minipigs fed a vegetarian, cholesterolfree diet. Total plasma cholesterol was measured in 26-week old LDLR+/+, LDLR+/-, and LDLR-/- Yucatan minipigs. Asterisks indicate p <0.01 (**) and p<0.001 (***) compared to LDLR+/+. Error bars represent SEM.
Coronary artery (Figure 2) displays human like atherosclerosis including hemorrhaging plaque.
Atherosclerotic Lesion Development (Figures 3–5): LDLR-/- minipigs fed a vegetarian, cholesterol-free diet develop atherosclerotic lesions on an accelerated timeline.
Figure 2. Atherosclerosis in the coronary artery of a 11-month old ExeGen® LDLR-/- minipig fed a Western-style diet.
Figure 3. Atherosclerotic lesions in the abdominal aorta of 7-month old ExeGen® LDLR-/- minipigs fed a vegetarian, cholesterol-free diet. Sudan IV-stained abdominal aortas from LDLR-/- (left) and LDLR+/+ (right) minipigs. Atherosclerotic lesions covered 86.2% of the abdominal aorta in an LDLR-/- minipig versus 0% in an LDLR+/+ minipig.
Figure 4. Atherosclerosis in the abdominal artery of a 11-month old ExeGen® LDLR-/- minipig fed a Western-style diet. Western diet included natural sources of cholesterol and fat.
Figure 5. Atherosclerosis in the abdominal artery of a 11-month old ExeGen® LDLR-/- minipig fed a Western-style diet. Hallmarks of human atherosclerosis, including raised lesions, smooth muscle proliferation, foamy macrophages, calcification and cholesterol clefts.
YUCATAN MINIPIG STANDARDS
|Normal Birth Weight||0.4 – 1.0kg|
|Normal Wean Weight||3.3 – 4.5kg|
|Weaning age||21-28 days|
|Sexual Maturity||6 months|
|Typical Weight at 6 Months||24.0 – 27.0kg (normal diet)|
|Typical Weight at 12 Months||44.0 – 51.0kg (normal diet)|
|Typical weight at 2 Years||84.0 – 98.0 kg (normal diet)|