18th International Mouse Genome Conference
17-22 October 2004, Seattle, USA
Plenary Presentations * Oral
Presentations * Poster
Abstracts * Photos
Verne Chapman Memorial Lecture * Table
of Contents * Attendees * Awards
ORAL PRESENTATION
WEDNESDAY OCTOBER 20
10.00am – 10.15am
CHARACTERIZATION OF THE MOM2 LOCUS: A SPONTANEOUS MUTATION RESULTING IN SUPPRESSION OF INTESTINAL POLYP FORMATION IN APCMIN MICE.
Buchberg AM, Silverman K, Koratkar R, Zeskind J, McEntee B, Baran A, Grant S, Siracusa LD
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, United States
We identified a new modifier locus of ApcMin-induced intestinal tumorigenesis called Modifier of Min 2 (Mom2), from a cross between DBA/2J (DBA) and C57BL/6J (B6) ApcMin/+ mice. The spontaneous Mom2 mutation most likely occurred in a B6 ApcMin/+ male. A single mutant Mom2R allele results in an ~90% reduction in small intestinal polyp number and colon polyp incidence in ApcMin/+ mice. We previously localized Mom2 to a 10 cM region on mouse chromosome 18, distal to the Apc gene. This region is syntenic with human chromosome 18q, which frequently undergoes loss of heterozygosity (LOH) in several human cancers, including colorectal cancer. An intercross between congenic DBA.B6 Mom2R/+ animals failed to generate mice homozygous for the Mom2R locus, indicating that Mom2R is a recessive embryonic lethal mutation. We describe an exclusion strategy for mapping the Mom2 locus, which relies on the lethal phenotype as a method of selection. Since the Mom2 region is highly conserved between the DBA and B6 strains, we established intersubspecific crosses between congenic DBA.B6 Mom2R/+ and Mus musculus castaneus mice to increase genetic diversity and facilitate the mapping of polymorphic markers to define the boundaries of the Mom2 region. The results further refine the chromosomal location of Mom2 to a 1 Mb gene-rich region. In addition, they suggest a probable mechanism of action for Mom2 in suppressing ApcMin-induced tumorigenesis. Efforts are underway to identify the gene encoding Mom2 and determine its involvement in human colorectal cancer susceptibility. Research supported in part by NCI PO1 CA72027.