Gender and genetic control of resistance to intestinal amebiasis in inbred mice

Resistance to the establishment of intestinal Entamoeba histolytica infection is dependent on the inbred mouse strain. In this work we used the inbred strains B6 (resistant), CBA (susceptible), B6CBAF(1) and a backcross of B6CBAF(1) to CBA to further examine the genetic basis of resistance. Mouse genotype was assessed with single nucleotide polymorphism and microsatellite markers and infection assessed by culture 9 days after intracecal E. histolytica challenge. The backcross population showed a male predisposition to culture positivity (P<0.002). F1 genotype at two loci on chromosomes 1 and 2 exhibited suggestive linkage with resistance to infection (P=0.0007 and 0.0200). Additional suggestive quantitative trait locus were observed on chromosomes 1, 9 and 13 for cecal parasite antigen load and histologic evidence of inflammation. Infection in C3H x B6 recombinant inbred mice supported the mapping data. Candidate B6 genes on chromosomes 1 and 2 were examined by microarray analysis of epithelial tissues from B6 vs CBA mice. This work shows a male predisposition to intestinal amebiasis and suggests that relatively few B6 loci can confer resistance in inbred mice. Future identification of regional candidate genes has implications for understanding the human variability to amebic infection.