Model systems Transgenic mice construction germline modification cloned gene (transgene) introduced into a fertilized mouse ovum constitutive non-specific insertion into genome conditional specific (targeted) insertion into genome the altered phenotype with the added gene is observed through the entire lifespan including embryonic development number of gene copies is variable altered phenotype passed to offspring as it is a germline mutation function studying dominant disorders due to the fact that the transgene will coexist with normal gene product Knockout mice construction similar to transgenic mice except instead of adding a foreign gene, a normal gene is removed also a germline modification function useful for studying loss-of-function mutations in human diseases Chimeric mice construction a genetic mix between two distinct cell lines fusion of two early embryogenic lines in embryogenesis two lines recognized as self due to absence of immune system function can reproduce to create offspring of various types in subsequent generations non-transgene homozygous transgene homozygous transgene heterozygous Cre-lox system construction a system that allows turning on/off of gene of interest with an antibiotic-controlled promoter function to study a gene whose deletion is lethal to embryos allows the embryo to develop to a certain stage and can then turn off a certain gene can also study the timing of when a gene is important in development RNAi construction dsRNA is synthesized complementary to the mRNA sequence of interest transfected into cells dsRNA separates and binds the complementary mRNA dsRNA (where one strand is the host mRNA) is seen as a viral product and degraded function ↓ expression of a particular gene