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Updated: Jan 5 2017

Biochemical Model Systems

  • 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
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