201910 In-Depth Phenotyping and Research Using IMPC-Generated Knockout Mouse Strains

Program seeks Council approval to reissue an initiative titled ‘In-Depth Phenotyping and Research Using IMPC-Generated Knockout Mouse Strains Exhibiting Embryonic or Perinatal Lethality or Subviability’.

The International Mouse Phenotyping Consortium (IMPC), of which the NIH Knockout Mouse Phenotyping Program-Phase2 (KOMP2) is a member, aims to create 20,000 knockout mouse strains over ten years for adult phenotyping. It is estimated that about 30% of these mice will die during the embryonic or perinatal periods. A large portion of homozygous lethal mutations also are expected to have viable heterozygous phenotypes. Developing a phenotyping pipeline for these mouse strains presents the scientific community with a unique opportunity since it will leverage the existing investment.

Embryonic lethal phenotyping is of strategic importance for several reasons. Most obviously, these genes are critical to embryonic growth, differentiation, and organogenesis.  Sixty-percent of all embryonic lethals exhibit abnormal anatomy. Mice with unique defects based on the timing of the lethal expression will be extremely useful as models for a range of congenital human diseases and birth defects. Viable heterozygote alleles are likely to be widely represented in human disease because of their haploinsufficiency or dominant phenotypic effects. So, there is significant and complementary value in also phenotyping heterozygote mutants for clinical phenotypes.

The objective of this initiative is to encourage applications to phenotype and/or perform research on embryonic lethal knockout (KO) mouse strains being generated through the IMPC-KOMP. This effort will be extremely important for identifying new genes and pathways controlling implantation and embryonic development and providing insight into genetic defects that might result in stillbirth, birth defects, as well as adult onset diseases. A condition of any award made through this funding opportunity would be to deposit data into the existing public databases coordinated through the IMPC, thus creating valuable resources for the scientific community.

This proposed concept falls under the auspices of the ‘Developmental Biology’ vision topic of NICHD.

Embryonic lethal mice are extremely useful models for a range of congenital human diseases and birth defects. Therefore, the concept fully aligns with the mission of the DBSV Branch.

Program Contact

Mahua Mukhopadhyay
Developmental Biology and Structural Variation Branch (DBSVB)

Back to Concept Review by Council

top of pageBACK TO TOP