All animal procedures performed in this study and described below were reviewed and approved by the pertinent Institutional Animal Care and Use Committees at the University of Pennsylvania and Harvard University and were consistent with local, state and federal regulations as applicable. Euthanasia in all instances was via terminal inhalation of carbon dioxide, consistent with the 2013 AVMA Guidelines on Euthanasia. C57BL/6J animals were obtained from the Jackson Laboratory (stock number 000664) and were bred in-house. Ldlr+/−;Apobec1−/−;Tg(APOB) mice, which were used to better model TG and LDL-C metabolism for genes in loci associated with one of those traits (Burkhardt et al., 2010), were bred in-house. rs27324996 knock-in mice and Angptl3 knockout mice were generated on the C57BL/6J background with CRISPR-Cas9 as described below and were bred in-house. All mice were fed a standard chow diet and maintained on a 12 hour light/12 hour dark cycle. Assignments to groups (experimental vs. control, comparisons between genotypes) were performed to achieve age-matched groups of littermates/colonymates with shared housing and were otherwise random. All mice used for experiments were healthy, free of drug exposure,
