With up to one third of knockout strains being embryonic lethal, a systematic unbaised phenotyping pipeline was established to perform morphologic and imaging evaluation of mutant embryos to define the primary perturbations that cause their death. From this important insights are gained into gene function.
IMPC centers funded by the NIH Common fund mechanism are delivering the following for All Lines:
- Viability
- Heterozygote E12.5 Embryonic LacZ staining ( 2 mutant animals, wt reference images)
For All Embryonic Lethal Lines, gross morphology is assessed at E12.5 to determine if defects occur earlier or later in development. A comprehensive imaging platform is then used to assess dysmorphology at the most appropriate stage:
| Procedure | Number | Note |
|---|---|---|
| E9.5 Gross morphology | at least 2 homs,2 wt | images optional |
| E9.5 OPT screening | at least 2 homs | reconstructions available |
| E14.5-E15.5 Gross morphology | at least 2 homs, 2 wt | images optional |
| E14.5-E15.5 microCT screening | at least 2 homs | reconstructions available |
| E14.5 HREM | at least 3 homs, 1wt | reconstructions available |
| E18.5 Gross morphology | at least 2 homs | images optional |
| E18.5 microCT | at least 2 homs, 2 wt | reconstructions available |
In addition, the NIH is supporting in-depth phenotyping of embryonic lethal lines with three current awardees.
Trevor William, University of Colorado School of Medicine
Jesse Mager, University of Massachusetts Amherst
Elizabeth Lacy, Memorial Sloan Kettering Cancer Center
Dr. Jeremy Reiter, University of California San Francisco