Nutritional Modulations Used to Translate a Rabbit Model of Atherosclerosis — A Systematic Review and Meta-analysis

Dietary cholesterol has been suggested as a cause of dyslipidemic atherosclerosis with scarce convincing evidence. A systematic review and a meta-analysis were conducted in MEDLINE (2004–2015) to screen randomized controlled trials (RCTs) that used cholesterol-fed rabbits as a model of atherosclerosis. A total of 32 RCTs (n = 1104 New Zealand rabbits; 4.37 ± 2.52 months old) reported lipid and lipoprotein outcomes following cholesterol intake (0.98 ± 0.67%) for a duration of 8.90 ± 7.26 weeks. Cholesterol intakes significantly raised combined lipid and lipoprotein outcomes (standardized mean difference) in a random-effect model by 5.618 (95% CI: 4.592, 6.644; P = 0.0001). The value of I2, heterogeneity, was 89.387%, indicating real variation. A subgroup analysis based on the duration and amount of cholesterol feeding in a mixed-effects analysis showed combined heterogeneous effects of 2.788 (95% CI: 2.333, 3.244; P = 0.000; Q = 112.206; df = 14) and 5.538 (95% CI: 4.613, 6.463; P = 0.000; Q = 31.622; df = 6), respectively. Random-effect meta-regression conducted using cholesterol moderator did not support causal effects of dietary cholesterol in inducing atherosclerosis, which may be due to significant publication bias. These high levels of heterogeneity among studies may decline fidelity of this animal model for translation of dyslipidemic atherosclerosis

Improving germline transmission efficiency in chimeric chickens using a multi-stage injection approach.

Although different strategies have been developed to generate transgenic poultry, low efficiency of germline transgene transmission has remained a challenge in poultry transgenesis. Herein, we developed an efficient germline transgenesis method using a lentiviral vector system in chickens through multiple injections of transgenes into embryos at different stages of development. The embryo chorioallantoic membrane (CAM) vasculature was successfully used as a novel route of gene transfer into germline tissues. Compared to the other routes of viral vector administration, the embryo's bloodstream at Hamburger-Hamilton (HH) stages 14-15 achieved the highest rate of germline transmission (GT), 7.7%. Single injection of viral vectors into the CAM vasculature resulted in a GT efficiency of 2.7%, which was significantly higher than the 0.4% obtained by injection into embryos at the blastoderm stage. Double injection of viral vectors into the bloodstream at HH stages 14-15 and through CAM was the most efficient method for producing germline chimeras, giving a GT rate of 13.6%. The authors suggest that the new method described in this study could be efficiently used to produce transgenic poultry in virus-mediated gene transfer systems