The Conditional Transgenic Mouse

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The Conditional Transgenic Mouse

• An Account of the Incredible Possibilities that
  Arise from an Intentionally Mutated Pest.
• William Radentz

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Making Research Easier

• Transgenic Mice are genetically engineered for
  your convenience.

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Transgenic Mice

• Chimeras and breeding, alleles and loci
• Targeting the desired gene
• --Homologous recombination in embryonic stem
  cells is standard for modifying the mouse genome
  at a specific locus.1
• --. In case recombination does not happen at the
  desired locus, ES cells showing resistance to the
  selective agent must also be screened PCR to
  reveal which clones have been correctly
  targeted.1

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Knock out and knock in Mice

• Genetic recombination allows for mice that can
  have specific genes upregulated (knock-in) or
  downregulated (knock-out).

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Regulation with Conditional Transgenics

• In order for researchers to study genes that are
  essential for development, a conditional
  transgenic KO of a gene has been developed to
  avoid problems that could arise from the
  modification of gene expression
• Inducible transgenics
• Virus activation
• Genetic construct
• Cre-lox technology

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Conditional KO

• Conditional gene modification using Cre-lox
  technology allows the gene of interest to be
  knocked-out in only a subset of tissues or only
  at a particular time, circumventing lethality 1
• Cre recombinase, a site-specific integrase
  isolated from the P1 bacteriophage, catalyzes
  recombination between two of its consensus DNA
  recognition sites 1

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only the finest in gene modification

• Conditional transgenic mice

Today, there is an abundant collection of mice
expressing Cre from a promoter that could be
1)tissue specific 2)cell specific 3)devolopmen
tally specific 4) responsive to an exogenous
agent ( ex Tetracycline)
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Risks of Playing God

• Animal models as a human models for disease
• If the protein being expressed from the transgene
  causes toxicity, excessive overexpression from
  multiple insertions can be lethal to some tissues
  or even to the entire mouse. For these reasons,
  several independent lines mice containing the
  same transgene must be created and studied to
  ensure that any resulting phenotype is not due to
  toxic gene-dosing or to the mutations created at
  the site of transgene insertion.1