Constitutive germline gene disruption via embryonic stem-cell homologous recombination or zygote CRISPR editing
pioneer
Mario R. Capecchi, Martin J. Evans, and Oliver Smithies (first recorded knockout mice, 1989; 2007 Nobel Prize)
Core Principles & Analysis
Mario Capecchi, Martin Evans, and Oliver Smithies created the first recorded knockout mice in 1989 by combining mouse embryonic stem cell culture with homologous DNA recombination, earning the 2007 Nobel Prize in Physiology or Medicine.
Comparing homozygous knockout (−/−) and heterozygous (+/−) mice against wild-type (+/+) littermates reveals whether a candidate drug target is essential for viability, fertility, metabolism, or behavior.
Phenotypes in knockout mice directly guided modern human therapeutics, from the extreme muscle hypertrophy of Mstn−/− mice to the severe hypercholesterolemia and atherosclerosis of Apoe−/− and Ldlr−/− mice.