A tissue-specific Knockout rat defines an animal model in which a gene of interest is "floxed" and thus inactivatable in specific cell types in a certain tissue (conditional). Other cell types and tissues exhibit an unmodified, functional gene expression.

This gene inactivation is achieved by an additional breeding step with a tissue- or cell type-specific Cre-deleter rat line. The creation process of such models also gives access to whole body (constitutive) Knockouts

Applications

For academic research:

  • Study gene function in one specific organ, tissue or cell type
  • Mimic pathologies caused by gene inactivation in a given cell type
  • Create a tissue-specific phenotype for multi-function proteins

For bio-pharmaceutical research & development:

  • Validate target genes with cell-specific functions
  • Investigate signaling pathways in certain cell types
  • Safety studies

Strengths of tissue-specific Knockout rat models

  • Very flexible: easy switch to study another tissue
  • High physiological relevancy of the obtained scientific data from such a model
  • Enables access as well to constitutive Knockout for comparison studies

Limitations of tissue-specific Knockout rat models

  • Rat line creation requires the insertion of exogenous sequences (loxP, FRT) that can deregulate transcription and splicing
    → Risk can be greatly minimized by applying in-depth bio-informatic, genetic, and bibliographic analysis
  • Few deleter rats are available, requiring the creation of new Cre-deleter rats
    → New tissue- or cell-specific Cre rat lines can be produced by genOway in parallel to the conditional rat model
  • Inactivation of the gene of interest in one cell type may occur during cell type differentiation, resulting in an impaired phenotype and/or modified cell physiology
    →  Limitation can be bypassed by applying conditions such as time-specific gene inactivation
  • To obtain tissue specificity, a crossing step with a deleter rat line implies a time-consuming production of cohorts
    →  This "time" issue must be anticipated and integrated in the scientific consulting prior to model development
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