Genetic control of myeloproliferation in BXH-2 mice.
While studying the unique Nramp1 (Slc11a1)-independent susceptibility to Mycobacterium bovis (BCG) infection of BXH-2 mice, we noted that these mice develop important splenomegaly and enlargement of lymph nodes. Segregation analyses in several F2 crosses showed that splenomegaly segregates as a single recessive trait caused by a novel mutation in BXH-2, independent of the infection. Histologic and fluorescence-activated cell sorter (FACS) analyses indicated that splenomegaly is associated with a large increase in Mac1+/GR1+ (macrophage antigen-1+/granulocyte differentiation antigen 1+) granulocyte precursors in spleen, lymph nodes, and bone marrow, resembling a myeloproliferative syndrome. This is concomitant to extramedullary erythropoiesis in the spleen, as measured by proportion of Ter119+ erythroid cells. The locus controlling this myeloproliferative syndrome and splenomegaly was designated Myls and maps to an 18 centimorgan (cM) region of chromosome 8, which also contains an integrated copy of an N-ecotropic murine leukemia virus (MuLV) provirus (Emv2). The relationship between Myls, expansion of Mac1+/GR1+ cells, and Emv2 was investigated. Homozygosity at Myls is necessary but not sufficient for B-ecotropic virus replication in splenocytes, the extent of which appears to be under separate genetic control. Our results suggest a model in which Myls-dependent myeloproliferation in BXH-2 acts as a predisposing factor for the subsequent development of virally induced myeloid leukemia characteristic of this strain.
Turcotte
Karine
K
Department of Biochemistry, McGill University, Montreal, QC, Canada H3G 1Y6.
Gauthier
Susan
S
Mitsos
Loukia-Maria
LM
Shustik
Chaim
C
Copeland
Neal G
NG
Jenkins
Nancy A
NA
Fournet
Jean-Christophe
JC
Jolicoeur
Paul
P
Gros
Philippe
P
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D027682:Cation Transport Proteins / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D009052:Leukemia Virus, Murine / Q000254:growth & development*; D007942:Leukemia, Experimental / Q000235:genetics* / Q000276:immunology / Q000821:virology; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis; D012192:Retroviridae Infections / Q000235:genetics* / Q000276:immunology; D013154:Spleen / Q000473:pathology; D013163:Splenomegaly / Q000235:genetics / Q000473:pathology; D014376:Tuberculosis / Q000276:immunology; D014412:Tumor Virus Infections / Q000235:genetics* / Q000276:immunology; D014779:Virus Replication; D000099173:Natural Resistance-associated Macrophage Protein 1
D027682:Cation Transport Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1