With years of experience in the field of genetically engineered model creation, Creative Biolabs is a trustworthy research partner for providing the most comprehensive and suitable mouse models for every specific requirement. Our battery of knock out mouse models includes conventional knock-out model, tissue-specific or inducible conditional knock-out models, and KO first models.

KO First (Conditional-Ready) Model

KO first model, also called conditional ready model, is a multipurpose mouse model generated with a modified conditional knock-out strategy. This time-saving strategy makes it possible to obtain a reporter gene knock-in model and conditional knock-out models simultaneously from a single project by breeding with the Cre/LoxP recombination system or Flp/FRT recombination system.

Mechanisms of KO First Model

Firstly, a vector with an frt-SA-IRES-Reporter-frt cassette inserted in the intron and a targeted Extron flanked by two loxP sites is used to disrupt the wildtype allele. As a result, the KO first mice is obtained with the target gene knocked out, a reporter gene and resistance gene knocked in. On one hand, targeted gene knock-out plus reporter knock-in models can be generated by breeding the KO first mice with Cre expressing mouse. With the help of reporter gene, the first model is useful in tracking the expression of the target knocked out gene, thereby facilitating gene study. On the other hand, by breeding the floxed mouse with the Flp expressing mouse, reporter cassette will be removed, and mouse with a conditional knock-out of the target gene can be obtained via exposure to tissue-specific Cre recombinases.

However, as with other conditional knock-out strategies, when designing the process of creating such a flexible model, careful considerations and extensive analysis are necessary in order to avoid down-regulated expression of the endogenous gene or truncated protein expression. Moreover, embryonic lethal phenotypes or expression dysregulation of other genes can occur, thereby calling for a thorough analysis of the potential risks.

The ‘KO first' Process

At Creative Biolabs, our highly-experienced technical team will carefully evaluate your project and find the most appropriate strategy for producing your mouse model. Once you approve the design, we'll generate the model following the below 5 steps:

  • Targeting vector construction
  • ES cell targeting and ES cell screening
  • Chimera production via blastocyst injection
  • Chimera breeding to germline
  • F1 mouse genotyping

Additionally, Creative Biolabs offers other types of knock-out models that you may also be interested in:

Contact us or directly send us an inquiry to design the most appropriate customized mouse model for your next project and beyond.

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