Gene Inactivation

Custom Knock Out Animal Models

Whether you need to determine the role of your gene in one or more cellular processes, gain important insights into mechanisms that underlie disease pathogenesis and prevention, or evaluate compounds to speed up the drug discovery process, Taconic Biosciences can help you create a custom knock out model for the therapeutic area or process you are studying.
Constitutive Knock Out:
Permanently inactivate a target gene in all cells of the body throughout development. Complete in approximately 38 weeks.

Constitutive Knock Out Allele

Conditional Knock Out:
Delete genes in a time- or tissue-specific manner in combination with the appropriate Cre recombinase-expressing mouse line. Complete in approximately 40 weeks.
Conditional Knock Out Allele
Taconic's multi-functional knock out (KO) targeting vector enables the generation of both constitutive and conditional KO mice. Conditional KO in a desired tissue or time is achieved through the use of Taconic's tissue-specific Cre or inducible CreERT2 mice.

Conditional Knock Out Allele

Constitutive KO with the Option for Conditional KO:
Save time and resources by generating the constitutive and conditional KOs from the same gene-targeting event. Complete in approximately 40 weeks.

Conditional KO with Cre-ER Gene Switch:
Use our proprietary Cre-ER technology to inactivate gene expression in an inducible manner at any stage of mouse development. Complete in approximately 40 weeks.
Give us a gene accession number and we’ll do the rest. Taconic's highly experienced design team will carefully evaluate your project and suggest the most appropriate strategy for humanizing your mouse.

Once you approve the design, we'll make the model:

  • Your targeting vector will be constructed with cloning technology that minimizes the introduction of unwanted mutations.
  • Your vector will be fully sequenced and electroporated into our highly germline competent C57BL/6NTac ES cells or one of a wide array of validated ES cell lines.
  • Clones thoroughly validated by Southern Blot will be injected into mouse blastocysts and transferred into pseudopregnant female mice.
  • The resulting chimeras will be bred to our highly efficient deleter mice to remove selection markers and achieve germline transmission in a single step. If necessary we can remove the selection marker in vitro already in the ES cells.

Strict quality control
We have rigorous processes in place to ensure you receive the model you requested:

  1. Validate all ES cells
  2. Perform health and genetic testing of all ES cell lines
  3. Generate Flp- and Cre-deleted lines.

In addition, you can get validated genotyping protocols for your mice.


Fast timelines
Taconic understands how valuable your time is and offers the fastest delivery times in the industry.

One point of contact
Get regular updates from your expert project manager—dedicated to your project—so you'll always know the status of your model generation.

Detailed milestone reports
Access detailed reports online on the progress of your project at the end of each milestone:

  • Targeting vector construction
  • Targeted and validated ES cells
  • Mouse model completion

Detailed Milestone Reports
Packages Include:
  • Documentation and verification of PCR-based genotype protocol
  • Coordinated transfer of donor males to Taconic's breeding facility in Germantown, NY.
  • Confirmation of genotype of donor males by PCR-based genotyping (max 2 alleles).
  • Rapid Expansion using C57BL/6NTac donor females.
  • Holding of excess donor males until offspring from rapid expansion are weaned.
  • Comprehensive health testing with breeding while waiting for results of IHMS-52 health testing.
  • PCR based genotyping of derived offspring (max 2 alleles).

Breeding to single gene homozygotes package includes:
  • Barrier breeding of derived offspring in a heterozygous x heterozygous mating format.
  • PCR based genotyping of offspring from heterozygous x heterozygous mating (max 2 alleles).
  • Initial cohort of animals ready for shipment from 5 weeks of age on.
  • Large Cohort 8-10/sex/genotype.
  • Small Cohort 4-6/sex/genotype.
  • Genotypes include homozygous, heterozygous, and wild type.

Notes:
  • Package ends when initial cohort is ready for shipping. Post Package breeding and fees will be based on your breeding plan.
  • Shipping charges from Taconic to customer are not included in package.
  • Package assumes receipt of 4 donor males from Taconic, additional services will be charged at catalog prices.
  • Pricing assumes genetic modification is not sex linked, Mendelian ratios will be obtained, 80% of female breeders will deliver live pups that survive until weaning, and an average litter size of 5 pups. Additional charges may apply if these conditions are not met.

Conditional with your Cre of interest package includes:
  • Barrier breeding of derived offspring heterozygous for the conditional allele with your Cre* line of interest.
  • PCR-based genotyping of offspring from above mating.
  • Barrier breeding of double heterozygous mice to generate appropriate experimental and control groups.
  • PCR-based genotyping of offspring from the above mating.
  • Initial cohort of animals ready for shipment at the beginning at 5 weeks of age.
  • Large package 8-10/sex/genotype.
  • Small package 4-6/sex/genotype.
  • Genotypes include homozygous for Cre-derived null deletion and wild type.

Notes:
  • Package ends when initial cohort is ready for shipping. Post package breeding and fees will be based on your breeding plan.
  • Shipping charges from Taconic to customer are not included in package
  • Package assumes receipt of 4 donor males from Taconic. Additional services will be charged at catalog prices.
  • Package assumes use of Taconic ubiquitous general Cre Deleter mice (12524-T) will be used for crossbreeding. Additional fees may apply if different Cre mouse is used.
  • Pricing assumes genetic modification is not sex linked, Mendelian ratios will be obtained, 80% of female breeders will deliver live pups that survive until weaning, and an average litter size of 5 pups. Additional charges may apply if these conditions are not met.
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