A constitutive Knockout rat, also referred to as conventional or whole-body Knockout (KO), defines a rat model in which the target gene is permanently inactivated in the whole animal, in every cell of the organism.

This gene inactivation is effective at all stages of development, from the one-cell embryo stage through adulthood.

Applications

For academic research:

  • Study/determine gene functions in the whole body
  • Mimic pathologies caused by whole body gene inactivation
  • Induce a phenotype to create a disease model or in vivoresearch tool

For bio-pharmaceutical research & development:

  • Validate target genes for strategies based on antagonist molecules
  • Study specificity and/or off-target activities of drug candidate (safety studies)
  • Develop new antibodies on the target protein

Strengths of constitutive Knockout rat models

  • Total absence of protein including all isoforms, or total absence of specific isoforms
  • Fast, and low risk, as a first solution for preliminary in vivo studies
  • Feasible in all genetic backgrounds

Limitations of constitutive Knockout rat models

  • Causes embryonic lethality in about 15% of all cases, when gene is involved in development
  • Impact on embryonic development may modify the animal physiology, adaptation and compensation mechanisms, resulting in false results
  • Phenotype obtained is the combination of different actions at different times in development, which may lead to inconclusive studies
  • →  Limitation can be bypassed by applying conditions such as time- or tissue-specificity
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