We propose to complete the development of a large series of RI strains formed from the intercross of LG/J and SM/J mouse strains. These strains have already completed two-thirds of the generations needed to reach effective inbred status. We will also score a large number of polymorphic microsatellite markers in these strains to genetically characterize them for our own work and the work of others using the RI strain set. In addition to developing RI strains, we will maintain an AI strain. This strain was formed by random mating from the same F2 population used in generating the RI strains. The combination of RI and Al strains from the same intercross will be a powerful resource for quantitative trait locus mapping for a wide variety of characters. We will test the RI strains for genetic variation in maternal effects on both neonatal and adult phenotypes using 40 reciprocal crosses between the RI strains and a standard inbred strain, C57BL/6J. In this design genetically different mothers give rise to genetically identical offspring so that reciprocal differences are due to genetic effects on the environment a mother provides for her offspring. In addition, we will test the """"""""thrifty phenotype"""""""" hypothesis that states that pre- and neonatal environment affects risk for diseases (hypertension, diabetes, obesity, coronary artery disease, etc.) in adulthood. Poorly nourished neonates adapt to low nutrition levels in utero and soon after birth. This adaptation persists into adulthood so they are particularly susceptible to the deleterious effects of a high fat diet later in life. The offspring from the reciprocal crosses will receive either a high or a low fat diet after weaning. We will test whether animals subjected to relatively poor pre- and neonatal environments respond more strongly to the high fat diet. We will map quantitative trait loci for these genetic maternal effects and their interaction with diet.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Resource-Related Research Projects (R24)
Project #
5R24RR015116-02
Application #
6540653
Study Section
Special Emphasis Panel (ZRR1-CM-8 (04))
Program Officer
Grieder, Franziska B
Project Start
2001-04-01
Project End
2004-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
2
Fiscal Year
2002
Total Cost
$344,136
Indirect Cost
Name
Washington University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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Cheverud, James M; Lawson, Heather A; Fawcett, Gloria L et al. (2011) Diet-dependent genetic and genomic imprinting effects on obesity in mice. Obesity (Silver Spring) 19:160-70
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Kenney-Hunt, Jane P; Cheverud, James M (2009) Differential dominance of pleiotropic loci for mouse skeletal traits. Evolution 63:1845-51
Wolf, Jason B; Cheverud, James M (2009) A framework for detecting and characterizing genetic background-dependent imprinting effects. Mamm Genome 20:681-98
Thach, B T; Kenney-Hunt, J P; Simon, T C et al. (2009) Sex-specific quantitative trait loci linked to autoresuscitation failure in SWR/J mice. Heredity (Edinb) 103:469-75
Reich, Michael S; Jarvis, Joseph P; Silva, Matthew J et al. (2008) Genetic relationships between obesity and osteoporosis in LGXSM recombinant inbred mice. Genet Res (Camb) 90:433-44
Leamy, L J; Klingenberg, C P; Sherratt, E et al. (2008) A search for quantitative trait loci exhibiting imprinting effects on mouse mandible size and shape. Heredity 101:518-26
Wolf, Jason B; Cheverud, James M; Roseman, Charles et al. (2008) Genome-wide analysis reveals a complex pattern of genomic imprinting in mice. PLoS Genet 4:e1000091

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