Model Creation with Charles River

Charles River Europe has joined forces with PHENOMIN-ICS, a scientific leader in functional genomics, to deliver a complete solution for mouse and rat model creation. Our combined in vitro and in vivo expertise provides an optimal environment for creating, validating, characterizing, preserving and distributing your transgenic and mutant rodent lines. PHENOMIN-ICS is considered a gold standard for successful germline transmission by the IMPC.

  • Homologous Recombination Models (Mice)
    • Design of an optimized strategy including prediction of off-target sites
    • Preparation of the construct(s) (targeted construct +/- CRISPR/Cas9* construct)
    • Electroporation in ES cell (C57BL/N, C57BL/6J** and BALB/cN
    • Microinjection of validated ES cells into defined blastocysts
    • Germline-transmitted F1 animals
    • Excision of the selection cassette (if required)

    ** Europe only
  • CRISPR/Cas9*- Generated Models
    • Design of an optimized strategy including prediction of off-target sites
    • Preparation of all materials for injection/electroporation
    • Injection/ electroporation of genetic materials to generate F0 mutated animals
    • Genotyping of F0 animals and delivery of F0 candidates
    • Off-target analysis in F0 founder animals (optional)
    • Germline breeding of F0 founders to achieve germ line transmission (optional)
    • Off-target analysis in germline transmitted F1 animals (optional)
  • Models That Can be Generated

    Mouse

    • Knockout: constitutive, conditional (tissue specific, inducible)
    • Knockin: reporter/tag, point mutation, humanization and Rosa26, Hprt
    • Structural variants including CNV
    • Transgenic: gene-overexpression


    Rat

    • Knockout: constitutive
    • Knockin: tag, point mutation
    • Structural variants including CNV


    Other options including 2-in-1 models (e.g., conditional humanization and knockout) are available.

    Contact us to discuss your project

  • Core Competencies
    • CRISPR/Cas9* validation: e.g. quantification of NHEJ or HDR events
    • Cre or creERT2 mediated tissue/cell deletion
    • Selection of transgenic line
    • mRNA expression validation e.g., validation of impact of complex mutations
    • Gene regulatory network evaluation
    • Viral transduction - in vivo
    • Biomarkers detection e.g., cancer cells
    • Validated mRNA panels e.g., cytokines and chemokines
    • Sequence of mutant allele
    • Precise CNV quantification by ddPCR
  • PHENOMIN-ICS Publications
    Variability in Genome Editing Outcomes: Challenges for Research Reproducibility and Clinical Safety
    Teboul L (1), Herault Y (2), Wells S (3), Qasim W(4), Pavlovic G(5)
    Molecular Therapy Vol. 28 No. 6 June 2020
    Optimizing PCR for Mouse Genotyping: Recommendations for Reliable, Rapid, Cost Effective, Robust and Adaptable to High-Throughput Genotyping Protocol for Any Type of Mutation
    Jacquot S(1), Chartoire N(1), Piguet F(2), Herault Y(1)(3), Pavlovic G(1).
    Curr Protoc Mouse Biol 2019 Dec;9(4):e65 
    Efficient and Rapid Generation of Large Genomic Variants in Rats and Mice Using CRISMERE
    Birling MC(1), Schaeffer L(1), Andre P(1), Lindner L(1), Marechal D(1), Ayadi A(1), Sorg T(1), Pavlovic G(1), Herault Y(1,)(2,)(3,)(4,)(5). Sci Rep 2017 Mar 7;7():43331 
    View a complete list of PHENOMIN-ICS publications

     

  • Genotyping

    PHENOMIN-ICS has more than 10 years of experience in providing robust, accurate, and fast results.

    • Genotype your transgenic line by a customized protocol PCR or qPCR on complex alleles or multiple regions of a locus for more in depth validation of a mutant model
    • Genotype your cohort by a high throughput protocol. Simplified genotyping with one qPCR on specific region to minimize costs for established and verified lines
    • Genotype your cryopreserved line (blastocysts and sperm genotyping)
  • Phenotyping

    Systemic phenotyping of mutant mice is crucial in order to understand the relations between genotype, phenotype and environment. With a comprehensive panel of phenotyping tests, we provide standardized and customized protocols. We have developed a battery of tests to address most of the biological functions and cover the main therapeutic areas:

    • Neurobiology and behavior platform: analysis of sensory responses, motor abilities, cognitive functions as well as behaviors related to neuropsychiatric disorders, such as anxiety, depression or schizophrenia. 
    • Metabolic exploration platform: detection of phenotypes in energy metabolism, glucose homeostasis, bone metabolism, renal and intestinal function.
    • Cardiovascular platform: detection of congenital heart disease, myocardial infarction, valve disease, cardiac hypertrophy, arrhythmias, hypertension and hypotension.
    • Oncology: various of engraftment, monitoring of tumor progression by in vivo imaging Clinical Chemistry platform: blood and urine analysis (clinical chemistry, hematology, immunology, endocrinology).
    • Histopathology and embryology: histopathological analyses of adult tissues and mouse developmental biology

 

About PHENOMIN-ICS

phenomin-ics logo

PHENOMIN-ICS, also known as the "Institut Clinique de la Souris," is a scientific leader in the field of phenogenomics. Based in Strasbourg, France, its mission is to support the academic community and commercial organizations by creating highly relevant, validated and robust animal models for research programs and drug development. With a unique set of core capabilities, they have developed over 2000 unique rodent models for leading universities, pharma and biotech companies around the globe.

PHENOMIN-ICS is an active member of the International Mouse Phenotyping Consortium (IMPC), which is dedicated to identifying the function of every protein-coding gene in the mouse genome.

 

Frequently Asked Questions (FAQs)

 

* CRISPR/Cas9 used under licenses to granted and pending US and international patents from The Broad Institute and ERS Genomics Limited.