KOMP2 mice phenotyping and availability

The ultimate goal of the Knockout Mouse Project (KOMP) and the Knockout Mouse Phenotyping Project (KOMP²) is to produce an invaluable resource for researching human disease and improving human health. This article describes how JAX is phenotyping 833 KOMP² strains and tells you how you can obtain KOMP ES cell lines and KOMP² mice.

The KOMP² phenotyping pipeline at JAX

The objective of the KOMP² project is to generate and phenotype 5,000 single-gene KO mouse strains from KOMP ES cell lines. The strains are phenotyped using protocols in a pipeline designed by the International Mouse Phenotyping Consortium (IMPC). There are three NIH-funded phenotyping centers in the United States: JAX, the BaSH Consortium (Baylor College of Medicine, the Wellcome Trust Sanger Institute and MRC Harwell), and the DTCC Consortium (University of California at Davis, the Toronto Center for Phenogenomics, Children’s Hospital Oakland Research Institute (CHORI) and Charles River ).

JAX’s objective is to phenotype 833 of the KOMP² strains. To do this, we are using a powerful and efficient high-throughput phenotyping pipeline that integrates recommendations from the IMPC and includes disease-relevant phenotypes recommended by a panel of internal and external KOMP² domain experts. The pipeline includes unique tests not mandated by the IMPC strategy. These tests add value to the characterization of each gene knockout. For each KO line, JAX is:

• Screening multiple organ systems for more than 200 phenotypes
• Quantitatively and qualitatively assessing each phenotype
• Delivering the phenotypic data to the KOMP² Data Coordination Center Database (DCCDB)

The following table outlines the phenotyping pipeline (mice are weighed each week):

Mouse age (weeks)	Phenotyping pipeline
4	Receive control and knockout test cohorts
4-7	Acclimate mice to test facility
8	Dysmorphology SHIRPA Grip strength
9	Open field * Light/dark * Holeboard exploration
10	Acoustic startle/prepulse inhibition
11	* Tail suspension Electrocardiogram * Rotarod
12	Glucose tolerance
13	* Plasma chemistries (lipids, glucose)
14	Body composition DEXA X-ray Eye dysmorphology survey (slit lamp, ophthamoscopy)
15	* Sleep
16	Auditory brainstem response Electroretinography
17	Seizure threshold
18	Hematology Clinical chemistries Histopathology and block banking Flow cytometry: spleen, * bone marrow

* Unique to KOMP² pipeline at JAX

Obtaining KOMP ES cell lines and mice

• ES cells for KOMP mice characterized by United States KOMP² centers are available from the UC Davis KOMP Repository.
• ES cells generated by other partners are available from the European Mouse Mutant Cell Repository (EuMMCR).
• Germplasm of KOMP strains will be available from these repositories once phenotyping is complete.
• To find a KOMP cell line and/or mouse distributor, search the International Mouse Strains Resource (IMSR).
• You can order breeder pairs of newly-produced mice from JAX during the approximately 18-week timeframe in which JAX is phenotyping them (availability depends on litter production above what is needed for phenotyping).

For more details on the KOMP and KOMP² projects, visit JAX’s KOMP website or the IMPC website.