Tissue-Specific Knockout Mice (Conditional)

A tissue-specific Knockout mouse defines a conditional biological model in which a target gene can be specifically inactivated in specific tissue(s); in all other tissues, the target gene exhibits a functional expression. genOway is able to target genes in most tissue types (e.g. brain, intestine, muscles, skin).

+   This strategy can bypass the limits that are usually observed with conventional Knockout (constitutive KO) models (e.g. embryonic lethality, compensatory mechanisms or complex phenotype). The phenotype can also be more reliably associated with inactivation of the target gene.
     
-   The design process of creating a tissue-specific Knockout model requires a thorough analysis in order to avoid endogenous gene deregulation or truncated protein expression. The timeline for this design is longer than with the conventional Knockout paradigm since the deletion of the gene requires an additional breeding step with a "tissue-specific deleter" mouse line.

Infographic: Tissue-specific Knockout mouse model

Custom Knockout Mouse Services at genOway

genOway provides a one-stop solution for the design, creation and analysis of your custom Knockout mouse model.

Step 1: Scientific evaluation

genOway has a dedicated team of scientists and bioinformatics experts who are able to perform thorough analyses of your project feasibility including:

  • Defining the model's objectives
  • Determining the characteristics of the target gene/locus
  • Analyzing data culled from the literature

Step 2: Design of genetically modified model

We evaluate the possible gene targeting options based on the results of the above scientific evaluation and present the design to the principal investigator with a clear assessment of model features, risks and timelines.

  • Our process guides you toward the best choice for your model design.
  • We provide free and non-binding access to this expertise.

Step 3: Production

genOway has an extensive background in genetically modified mouse technology and will provide you with the highest quality product possible. Four mouse Knockout production options are available. All options include the same dedicated customer support.

Option 1:  Full service

Your project is managed from initial conception to final realization by our in-house transgenesis experts. This level of service includes:

  • Model design, starting from a gene accession number
  • Model creation up to validated heterozygous/homozygous animals
  • Cohort production
  • Phenotyping  (i.e. physiological validation of the model along with a comprehensive array of tests)
Option 2:  Standard service

genOway manages your project from initial conception (starting from a gene accession number) to the delivery of heterozygous animals.

Option 3:  Partial production service

Exit the model creating process at any step of your choosing (such as vector construction or recombined ES cell line creation).

Option 4:  Animal production service

A) By homologous recombination: genOway manages your model creation project, starting from existing targeting vectors or ES cell clones. These vectors or clones are either developed in your lab or available via the International KO Mouse Consortium (IKMC – EUCOMM, KOMP, NorCOMM).

Milestones Full Standard Partial production Animal production
Project evaluation Bioinformatics analysis, bibliography search,
project feasibility assessment
Analysis of the selected strategy,
risk assessment
Model design and targeting
vector construction
x x x  
Recombined ES cells x x optional optional
Blastocyst injection x x optional x
Heterozygous animals x x   x
Homozygous animals x optional   optional
Cohort production x optional   optional
Phenotyping x optional   optional

 

B) By CRISPR/Cas9 nuclease system: genOway manages your model creation project, starting from existing material either developed in your lab or available via third-party providers.

Milestones Full Standard Partial production Animal production
Project evaluation Bioinformatics analysis, bibliography search,
project feasibility assessment
Analysis of the selected strategy,
risk assessment
Model design and nuclease
production
x x x  
Injection into
fertilized embryos
x x optional x
3 independent founders x x   x
Homozygous animals x optional   optional
Cohort production x optional   optional
Phenotyping x optional   optional

Genetic Background

A) For homologous recombination. ES cell lines are currently available for the following genetic backgrounds:
C57BL/6N, C57BL/6J, BALB/c, 129Sv, 129Ola

Our ES cell lines have been validated for germline transmission after 2 rounds of electroporation.

B) For CRISPR/Cas9 nuclease system. We have extensive experience applying CRISPR/Cas9 nuclease technology to virtually any genetic background using specifically adapted protocols and procedures.

Guarantee

Our guarantee comprises:

  • Generation of chimeras
  • ES cell germline transmission
  • Off-target measurement
  • Developmental deadlines
  • Confidentiality
  • Exclusivity of intellectual property
  • Breeding under VAF Elite/SOPF conditions: the health status is issued by professional breeders (such as Charles River)
  • Line importation and worldwide delivery of the line using a professional transport network

Benefits of Entrusting Your Model Development Project to genOway

Expertise

  • More than 1,500 models generated so far
  • Strong consulting activity provided for model design
  • Thorough project assessment prior to project start

Quality controlled production

  • Robust and validated technologies
  • Clear cut guarantees
  • No waiting list

Project management and reporting

  • A dedicated PhD project manager
  • Rigorous and regular reporting
  • On-site meetings

Unique IP positioning

  • Access to exclusive licenses for key technologies
  • Customer retains all the IP on the model
  • No claim, no royalty, no follow-on rights by genOway