International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 116 - GENETIC CONTROL OF SPLENOMEGALY AND EXTRAMEDULLARY HEMATOPOIESIS IN THE BXH2 MOUSE STRAIN

K Turcotte
McGill University

1) Gauthier S, 2) Shustik C, 3) Jolicoeur P, 1) Gros P
1) McGill University, 2) Royal Victoria Hospital, 3) IRCM, Universite de Montreal

BXH2, a recombinant inbred strain derived from C57BL/6J and C3H/HeJ, develops a spleen hyperplasia that is absent in either of the parental strains. The genetic basis of this splenomegaly was investigated in mice derived from crosses between BXH2 (spleen index 1.07 0.10) and either C57BL/6 (spleen index 0.693 0.05), BALB/c (spleen index 0.73 0.05) or A/J (spleen index 0.53 0.05). All the F1 mice showed low spleen indices (0.62 0.10). In (BALB/c X BXH2)F2 mice, 75 of 340 (22%) showed high spleen indices ( 0.8). In (A/J X BXH2)F2 mice, it was 49 of 385 (13%). Whole genome scan was performed on 187 mice using polymorphic markers spaced at approximately 10cM from each other. Strong linkage was detected on distal portion of chromosome 8 (LOD 43). Histology analysis of spleens, bone marrow and lymph nodes suggest an extramedullary hematopoiesis as the cause of the splenomegaly with abundant neutrophils detected in the spleen, the bone marrow and the lymph nodes. FACS analysis showed a 3 fold increase (from 3% to 9%) of Mac-1/GR-1 (graulocytes) and a 2 fold increase (from 3% to 7%) of TER 119 (erythroid cells) in the big spleens. In the bone marrow, a 1.5 fold increase (from 47% to 73%) of Mac-1/GR-1 and a 3 fold decrease (from 29% to 9%) of TER 119 was observed in the same mice. Our findings suggest that a new locus on chromosome 8 plays a regulatory role in hematopoiesis in general and granulopoiesis in particular.


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