ES Cell to Mouse Service

Create or import a mouse made from embryonic cells

The APN provides this service at Monash

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The ability to genetically modify mice is a powerful tool used in basic and applied research with many applications for the study of gene function and human disease. A current world-wide initiative is generating a knockout mouse strain for every protein coding gene using embryonic stem (ES) cells. Mouse strains and ES cells from these initiatives are made available to the worldwide research community via public repositories.

Once phenotyped, mouse models provide invaluable insights into human gene function with wide-ranging clinical implications, including better understanding of diseases and discovering gene targets for therapeutic agents.

The Embryonic Stem (ES) cell to Mouse (ES2M) service is a core APN facility which provides ready access to the global initiative to discover functional insight for every gene by generating and systematically phenotyping 20,000+ knockout mouse strains. The ES2M service enables Australian researchers to choose the genetically modified ES cell line(s) or mice of interest and lodge a request. The ES2M service will do the rest – delivering researchers heterozygous genetically modified mice to their facility ready to advance their research.

CRISPR gene editing

CRISPR is new and transformative technology that allows researchers to generate bespoke animal models to examine gene function and disease drivers.

The APN provides this service at ANU, Monash, SAHMRI, WEHI.

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CRISPR genome engineering provides ready access to technologies capable of modifying the genome of animals through injection of CRISPR/Cas9 reagents.  Genetically modified animal models play a key role in the understanding of gene function, human development and disease.  The APN was an early adopter of CRISPR/Cas9 genome editing – an efficient way of generating custom animal models – making it one of the first not-for-profit services offering this type of genome editing to Australian researchers.  CRISPR/Cas9 offers advantages over the traditional ES cell approach in that founder mutants are generated rapidly.

To meet the high demand for this fast, affordable, versatile and reliable platform, the APN offers CRISPR genome editing services through four nodes across Australia. With our collective experience and expertise in a wide variety of projects, one of APN’s CRISPR teams can assist in the production of genetically modified animal models using mice, rats and rabbits.

Missense Mutation Library

The ENU gene variant collection uses the alkylating agent N-ethyl-N-nitrosourea (ENU) to induce random point mutations in the mouse genome that can be highly reflective of human monogenic (single gene) diseases. The APN produces a diverse experimental mouse resource of missense gene variants, where that genetic variation can be limited on an otherwise inbred strain background and where the tools of experimental biology can be applied to full effect.  Many missense mutations produced by ENU yield unique counterparts of human variation, illustrated for example by analysis of the effects of quantitative variants in Zap-70, Ligase 4 and Ikappa kinase gamma.

The APN provides this service at ANU

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MML Logo  As G1 mice are subjected to whole exome sequencing, large numbers of ENU-induced mutations are detected within and near coding exons. Mutations are computationally analyzed and those that cause coding change or occupy splice junctions (defined as nucleotides ≤ 10 residues from the exon boundary) are flagged for export to the Missense Mutation Library.

Each SNV is given a unique identification number. The gene, chromosome and exact location (Ensembl coordinates), amino acid change or distance from the splice junction, Polyphen2 score, SIFT mutation prediction analysis are listed in sortable columns. All missense mutations are analyzed using Polyphen2 and SIFT (altered to use mouse sequence databases) to predict the effect of the variation on the protein. A computational pipeline adds further annotation, including links to Mouse Genome Informatics (MGI), Human Rare diseases (Orphanet), and gene expression links to Immgen and Gnf.  SNV availability indicates whether the SNV is in a mouse that is cryopreserved or still breeding in the facility and source of the SNV.

Collaborative Cross Mice

New Service.  The APN, through its ANU node, offers a unique collection of Collaborative Cross animals as generated by a consortium of groups since 2004.  The Collaborative Cross animals were developed to investigate multigenic traits not impacted by the stringent breeding controls in commonly used inbred lines.

The APN provides this service at ANU

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Imported from the University of North Carolina, we currently have approximately 30 lines available.  Orders must be placed in advance to allow for breeding of animals to supply levels.

For more information on the Collaborative Cross see http://csbio.unc.edu/CCstatus/index.py

Special Introductory Pricing: $50 per animal (Prices subject to change, this is an introductory price only correct as of 30th August 2016).

Please note the APF do no currently offer the distribution of the parental lines which you may like to utilise for control purposes. You may contact UNC or Jax for importing these lines or APF may be able to provide Quarantine Services for the importation of these lines if required. Please contact us for more information

The APF can also provide phenotyping services on the Collaborative Cross lines at our facility.

Please contact us at: Apf.scientific.programs@anu.edu.au for more information on the Collaborative Cross.