Phenotyping pipeline design


Broad phenotypic characterization of emerging mouse models will add important value and greatly enhance their utility to the scientific community. The extensive library of single-gene knockout strains generated through the KOMP program will become significantly more valuable with comprehensive assessments of the functional consequences of removing one gene. 

Effective high-throughput mouse phenotyping is therefore critically important to establish baseline genotype/phenotype understanding for functional analysis of the KOMP resource. The Jackson Laboratory KOMP2 Phenotyping Center provides a powerful and efficient phenotyping pipeline to assess the physiological, behavioral and morphological effects of eliminating a single gene.

The JAX KOMP2 Phenotyping Center will:

  • Screen multiple organ systems in 833 knockout lines for more than 200 phenotypic traits.
  • Determine quantitative and qualitative assessment of phenotypes for each mutant line using automated calling procedures and technical, statistical and scientific review. Scientific review comprises evaluation of composite phenotype profiles in a “grand rounds” approach to produce a comprehensive evaluation of each mutant strain.
  • Deliver per-mouse phenotypic data to the KOMP2 Data Coordination Center Database (DCCDB).

Phenotyping pipeline design

The JAX KOMP2 pipeline design is based upon previous large-scale, high-throughput phenotyping programs carried out at The Jackson Laboratory, selecting from them the most successful and high-throughput procedures. We have also integrated global recommendations of the International Mouse Phenotyping Consortium (IMPC), which identified important parameters that will collectively summarize the consequences of removing the function of a single gene in the context of the whole animal. The pipeline also includes additional disease-relevant phenotypes based on proven protocols and expertise from additional internal and external investigators that comprise our panel of JAX KOMP2 Domain Experts.

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

*Unique to JAX KOMP2 pipeline