Understanding Gene Function and Molecular Bases of Disease using Transgenic and Gene Targeting Technology: The Transgenic Core Facility
Background
The next major frontier for discovery is defining the function of genes, finding disease genes and understanding disease mechanisms. An integral part of this next research frontier is the use of genetically modified mice and in vivo models.
The Transgenic Core Facility: 1999 to present
The transgenic core facility (TCF) was established under the support of the Research Grants Council between 1999-2006. It is currently supported by University Grants Council AoE programme "Developmental Genomics & Skeletal Research".
Apart from supporting the research projects in the Aoe programme, the TCF also provides service to others. From its inception it has supported others. To date the TCF has:
- generated 70 vectors for gene targeting and transgenic mice;
- generated 44 knockout/knock-in mice; 32 new lines of transgenic mice;
- imported, rederived and established 52 lines of transgenic/mutant mice;
- initiated a major cryopreservation programme to preserve mouse lines;
- provides training in the form of hands-on training to many students and investigators.
The PIs supported by the TCF past and present are from the Departments of Biochemistry, Medicine, Paediatrics, Pathology, Obstetrics & Gynaecology, Surgery, Zoology. The TCF has now supported the transgenic/knockout aspects for 23 RGC-funded projects, three RGC Group Research projects and the AoE programme.
Current mode of operation and cost recovery
The TCF operates by partial cost recovery. The following information may be helpful to you if you are considering making genetically modified mice and would like TCF support. Prof. Cheah and the TCF team provide help with designing the targeting vectors, provision of reagents. For KOs, the cost includes generating the ES clones for up to three electroporations, selection of ES clones for screening, karyotyping targeted clones; generation of chimeras from two clones (up to 10 blastocyst injections total). At least 3-5 chimeras will be needed for breeding for germline transmission. The PI will be responsible for making the targeting vectors, genotyping/Southern blot analysis of the picked ES clones, and genotyping mice using tail tips provided by the TCF.
If a PI would like the support of the TCF for making KOs, the cost is $100,000 and is added to the budget of the grant proposal. The cost is to cover consumable supplies for making the mice, animals and part of the salary cost. This arrangements is very cost effective considering the separate cost in terms of time and expertise that would be involved if the PI were to recruit and have trained, a separate researcher to perform the technically challenging task of producing knockouts. Apart from the generation of the mice, Prof. Cheah and the TCF team also provide help with designing the transgenic or targeting vectors, provision of reagents. The TCF also provides other services such as embryo rederivation, cryopreservation, in vitro fertilization. Interested PIs may contact Prof Cheah biochem@hkusua.hku.hk for information.