ExeGen LDLR

-/-

Homozygous Genotype

This model features targeted disruption of the endogenous LDLR (low-density lipoprotein receptor) gene in Yucatan miniature swine genetics.

Background

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

Hypercholesterolemia
Characteristics:

ExeGen® LDLR-/- Yucatan MiniSwine 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 MiniSwine fed a vegetarian, cholesterolfree diet. Total plasma cholesterol was measured in 26-week old LDLR+/+, LDLR+/-, and LDLR-/- Yucatan MiniSwine. Asterisks indicate p <0.01 (**) and p<0.001 (***) compared to LDLR+/+. Error bars represent SEM.

Atherosclerosis Characteristics:

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-/- MiniSwine fed a Western-style diet.

  • Figure 3. Atherosclerotic lesions in the abdominal aorta of 7-month old ExeGen® LDLR-/- MiniSwine 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-/- MiniSwine versus 0% in an LDLR+/+ MiniSwine.

  • Figure 4. Atherosclerosis in the abdominal artery of a 11-month old ExeGen® LDLR-/- MiniSwine 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-/- MiniSwine fed a Western-style diet. Hallmarks of human atherosclerosis, including raised lesions, smooth muscle proliferation, foamy macrophages, calcification and cholesterol clefts.

YUCATAN MINISWINE STANDARDS

Normal Birth Weight 0.4 – 1.0kg
Normal Wean Weight 3.3 – 4.5kg
Weaning age 21-28 days
Gestation 114-116 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)