eNews February 12, 2013

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.