International Mammalian Genome Society

The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

E15 Modifiers of Egf-Receptor Phenotype

Green, P.1, Threadgill, D.2, Yee, D.1, Om, J.1, Thiele, B.1, Schork, N.1 and T. Magnuson1. 1 Case Western Reserve University, Cleveland, OH 44106 and 2 Vanderbilt University, Nashville, TN

Microsatellite marker mapping was used to study the genetic complexity underlying phenotypic differences of the EgfrTm1mag null allele on different genetic backgrounds. The Egfr null phenotype varies with genetic background. On a 129/Sv background, homozygotes die midgestationally due to placental defects, but on a CD-1 background, homozygotes die perinatally. Furthermore, the CD-1 effect is dominant since intercrosses between these two strains leads to perinatal lethality. From an F1[CD-1 X 129Sv] EgfrTm1mag/+ backcross to 129/Sv approximately 5.6% of all progeny are surviving homozygotes, which suggests that approximately 2-3 dominant modifiers mediate perinatal survival. To map these modifiers, DNA collected from homozygotes that survive the midgestational lethality (called 'rescues') as well as resorbing homozygotes (called 'non-rescues') from this cross was analyzed. A genome scan of 30cM intervals on 28 rescued progeny and 54 non-rescued progeny identified 4 CD-1 regions that co-segregate with the rescue phenotype. One CD-1 genomic region was negatively correlated with rescue. Each region is statistically significant (p<.05) when point-wise comparisons are made with non-rescues. However, study of an additional 30 rescue progeny did not increase statistical significance of these regions. Currently, phenotypic effects of Egfr mutation on several inbred lines are being studied.


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