The objective of this K0MP2 project is to provide comprehensive phenotyping of 200 KOMP mutant mouse lines each year for five years. This will provide significant new information regarding gene function, especially for un-annotated genes, to the research community and will accelerate our understanding of the genetic basis of disease. This goal will be achieved by a consortium having a significant track-record in mutant mouse production, phenotyping, technical innovation and working together on collaborative projects. The UCD-TCP-CHORI consortium consists of the Mouse Biology Program at U. California Davis (UCD), the Toronto Center for Phenogenomics (TCP), and Children's Hospital of Oakland Research Institution (CHORI). In this application, we propose phenotyping 200 homozygous K0MP2 mutant lines each year: 150 adult mutant lines will be phenotyped at the UCD - CHORI site using a single pipeline approach and integrating molecular phenotyping into the assessment;and 50 sub-viable lines will be phenotyped at TCP along with adult phenotyping of heterozygotes for a subset of the embryonic lethal lines. In addition, TCP will assess homozygous mutant adult lung function using a well established challenge test in a subset of the adult-viable mutant lines. Methods, procedures-and best practices for adult phenotypes shared among the UCD-TCP-CHORI consortium members will be harmonized. The plan integrates well with the recommendations of the International Mouse Phenotyping Consortium, but we have recommended changes that will save significant resources, and provide rich novel datasets. Innovations include: A) a single pipeline approach for the adult-viable lines;B) intensive and detailed embryonic lethal phenotyping that incorporates several imaging modalities;C);targeted sub-viable mutant phenotyping;and D) intelligent transcriptome analyses in homozygous adult. Also, we propose an intensive technology development program to apply the revolutions in DNA sequencing technology to refine, tailor and optimize RNAseq for transcriptome analyses and to explore other molecular phenotypes such as micro RNA profiling, and metabolomics for future incorporation into the phenotype screens.

Public Health Relevance

Mutant mice are an essential tool for understanding the function of genes and the mechanisms by which genetic variation affects disease risk in humans. This project will generate valuable data about gene function by characterizing the changes due to mutations in specific genes.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HG006364-04
Application #
8719761
Study Section
Special Emphasis Panel ()
Program Officer
Fletcher, Colin F
Project Start
2011-09-16
Project End
2016-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
4
Fiscal Year
2014
Total Cost
$3,391,356
Indirect Cost
$533,529
Name
University of California Davis
Department
Surgery
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Wong, Michael D; Maezawa, Yoshiro; Lerch, Jason P et al. (2014) Automated pipeline for anatomical phenotyping of mouse embryos using micro-CT. Development 141:2533-41
Adissu, Hibret A; Estabel, Jeanne; Sunter, David et al. (2014) Histopathology reveals correlative and unique phenotypes in a high-throughput mouse phenotyping screen. Dis Model Mech 7:515-24
Takeo, Toru; Fukumoto, Kiyoko; Kondo, Tomoko et al. (2014) Investigations of motility and fertilization potential in thawed cryopreserved mouse sperm from cold-stored epididymides. Cryobiology 68:12-7
Li, Ming-Wen; Vallelunga, Jadine M; Kinchen, Kristy L et al. (2014) IVF recovery of mutant mouse lines using sperm cryopreserved with mtg in cryovials. Cryo Letters 35:145-53