Quality management coordinator:
Dr. Helmut Fuchs
National Research Center for Environment and Health (GSF), Neuherberg near Munich
Phone: +49 89 3187 3151
E-Mail: h.fuchs@gsf.de
Quality Management "Animal Models"
The working group "Animal Models" has standardised animal house procedures and conditions in order to minimise variability in experiments. Standards developed by these working group include aspects of work step in the laboratory, phenotpying tests applied on the mice, mouse husbandry and hygienics, and exchange and shipment of mice between institutes.
The working group "Animal Models" is tightly associated with the European research programme Eumorphia and is using the European Mouse Phenotyping Resource of Standardised Screens(EMPReSS). This is a comprehensive database of validated SOPs for systematic screens and test that allow to describe the phenotype of a mouse. The SOPs are developed by scientist of leading genetics research institutes across 8 European countries.
The protocols are validating and ranked by three levels: gold, silver and bronze. The rating „Bronze“ is given after validation by testing on selected inbred mouse strains and/or selected mutants at one EUMORPHIA laboratory. The ratings „Silver“ and "Gold" are given after validation by testing on selected inbred mouse strains and/or selected mutants at two and more than two EUMORPHIA laboratories, respectively. A list of these protocols can be found on the website of the Eumorphia project.
In the primary screen mice move through the GMC and are examined sequentially in up to 12 of 14 screens. A comprehensive workflow manage¬ment has been established for a coordinated characterization of batches of mutant and control mice. To achieve a maximum gain of phenotypic result data with a minimum number of animals the chronology of the examinations performed sequentially on the same animals is arranged in a standardized workflow.
An IT-based clinical information system has been implemented which includes an advanced management of all kind of animal and facility data. A graphical user interface enables the users to interactively enter and retrieve all kind of data generated inside the German mouse clinic (GMC). The GMC IT system consists of several modules. The software allows for the interactive input of animal and facility based data: Matings, litters and weanings can be entered and processed. Full genealogic trees including mouse core data and phenotyping results can be shown in a genealogy browser and can be exported. When a batch of new mice is imported into the GMC from other mouse facilities the basic data of these mice (like birth date, gender, genetic background, ear tag, coat colour, etc.) can be easily imported into the GMC database from a standardized Excel interface. Mice can be assorted to groups for any purpose to facilitate e.g. the workflow management of these mice or the export of result data to Excel files.
The working group "Animal Models" is tightly associated with the European research programme Eumorphia and is using the European Mouse Phenotyping Resource of Standardised Screens(EMPReSS). This is a comprehensive database of validated SOPs for systematic screens and test that allow to describe the phenotype of a mouse. The SOPs are developed by scientist of leading genetics research institutes across 8 European countries.
The protocols are validating and ranked by three levels: gold, silver and bronze. The rating „Bronze“ is given after validation by testing on selected inbred mouse strains and/or selected mutants at one EUMORPHIA laboratory. The ratings „Silver“ and "Gold" are given after validation by testing on selected inbred mouse strains and/or selected mutants at two and more than two EUMORPHIA laboratories, respectively. A list of these protocols can be found on the website of the Eumorphia project.
In the primary screen mice move through the GMC and are examined sequentially in up to 12 of 14 screens. A comprehensive workflow manage¬ment has been established for a coordinated characterization of batches of mutant and control mice. To achieve a maximum gain of phenotypic result data with a minimum number of animals the chronology of the examinations performed sequentially on the same animals is arranged in a standardized workflow.
An IT-based clinical information system has been implemented which includes an advanced management of all kind of animal and facility data. A graphical user interface enables the users to interactively enter and retrieve all kind of data generated inside the German mouse clinic (GMC). The GMC IT system consists of several modules. The software allows for the interactive input of animal and facility based data: Matings, litters and weanings can be entered and processed. Full genealogic trees including mouse core data and phenotyping results can be shown in a genealogy browser and can be exported. When a batch of new mice is imported into the GMC from other mouse facilities the basic data of these mice (like birth date, gender, genetic background, ear tag, coat colour, etc.) can be easily imported into the GMC database from a standardized Excel interface. Mice can be assorted to groups for any purpose to facilitate e.g. the workflow management of these mice or the export of result data to Excel files.
Using this IT system the experiments are planned weeks in advance to support the users in arranging their phenotyping slots. Work lists are printed out for the daily work in the lab. Color-coded cage cards are used to describe the cage mates.
Results stored in flat files or transferred via interface devices are parsed and checked for input errors by a variety of scripts. Raw data are not stored in the database. The final validation of the data is performed by the scientists on the level of Excel files. Examination parameters are mostly grouped to parameter sets consisting of up to 50 parameters. The results are extracted from individually formatted files and passed over to central data interfaces (e*Gate Integration Suite) by VBA scripts. Before inserting the results into the GMC database checks for plausibility and referential integrity are automatically performed. Currently approx. 425,000 result datasets from more than 4,000 mice are stored in the database. This is on average 104 (minimum 1, maximum 351) parameters per mouse. Forms for an assisted manual input and display of results of the phenotype analysis for a certain mouse are established. Interfaces for the data export to Excel files (e. g. for a detailed statistical analysis of phenotype data or work lists for the input and upload of result data) are available. The results of the examinations in the primary screens are accessible to all GMC screeners. Therefore the results can be viewed from different scientific perspectives which allows a more comprehensive assessment of the phenotypes and their possible causations and relations to each other. Screeners can easily create individual ad-hoc queries to the database using the tool “Querybuilder” to retrieve information which are not directly available from the graphical user interface. For this neither inside knowledge of the database schema (including primary key / foreign key relations) nor the query language SQL is needed. Almost all relevant information can be selected or used as restrictive conditions with a few mouse clicks. So the users are not limited to pre-defined queries. Even aggregate functions, sorting and complex conditions (logical AND and OR in one query) are available. The corresponding SQL command is generated automatically and executed directly or after a manual modification. The result set can be exported to an Excel file or it can be further processed within the software. Some experiments require an official approval and are limited to a certain number of animals. A tool for the automatic calculation of the number of animals housed in the GMC in a given period of time grouped by particular criteria (e. g. gene¬tically modified animals or animals in an experimental state) is available. This will facilitate the calculation and increase the accuracy of animal numbers reported to the regulatory authorities. Movements of mice between cages inside the facility are stored in the database. The animals are located in individually ventilated cages. The hygienic status of the IVC racks is monitored by soiled air/bedding-sentinel mice. Using these information it is possible to detect animals potentially affected from infectious diseases or seized with parasites. In the past in spite of the mandatory health monitoring of animals according to the FELASA recommendations prior to the import a batch of mice was affected by helminths. Using the movement and sentinel data we could quickly identify the affected mice and prevent a propagation of the helminths to other animals (3). The application is running on a scalable Windows 2000 terminal server farm. It is available from any operating system on the client computers via Citrix MetaFrame XPa technology. This technology also provides a management console which enables administrators to shadow client sessions running on the server and even taking over control (if the user agrees). Thus an administrator can offer quick remote assistance to the users without physically entering the hygienically sensitive mouse facility. A relational database linked to the application is used as a central data store. To prevent data loss from local hard disk drives we store the files on a central file server. Recently the amount of hard disk storage capacity available to the members of the institute and the GMC on a central “Network Attached Storage” (NAS) RAID system has been increased to > 1 TByte. On the NAS, differential snapshot backups and full backups to tape are performed 3 times a day or once a week, respectively. Former versions of up to one month old files can be restored easily. User- and / or group-specific access authorisation privileges can be assigned to the directories. The NAS system itself is administered by the GSF computer center. The GMC IT group sets up the directories, organisational groups and access privileges for the projects of the institute within the GSF Active Directory Domain. The NAS will be used as a high-availability system for the storage of any kind of files, even large files like videos or images from X-Ray scanners or our Micro-Computer Tomography machine.
previous |