Hematopoietic stem cells and myeloid precursor cells in nonobese diabetic (NOD) mice.
Expression of diabetes susceptibility genes at the hemopoietic stem cell level is sufficient for the development of the disease in nonobese diabetic (NOD) mice. This work investigated whether the defects that reside within the stem cells have consequences on the homeostasis of the stem and progenitor cell compartments. The fraction of cyclically active stem cells, or spleen colony-forming units (CFU-s), is enlarged, and their differentiation toward megakaryocytopoiesis seems to be enhanced in NOD mice at 3 and 10 weeks of age as compared to C57BL/6 mice. Whereas colony-forming unit assay (CFU-A) numbers are normal in the bone marrow, they are significantly increased in the spleen of NOD mice. A strain-dependent difference in granulocyte-macrophage colony-forming cell (GM-CFC) numbers was observed; they were higher in NOD mice than in B6 mice of three and ten weeks of age. These results suggest that autoimmune type 1 diabetes mellitus of the NOD mouse is accompanied by disorders of myelopoiesis and megakaryopoiesis. This observation is in keeping with the role of macrophages in the development of diabetes and with the hyperactivity of diabetic platelets.
Lepault
F
F
CNRS URA 1461, Hôpital Necker, Paris, France.
Gagnerault
M C
MC
Dardenne
M
M
Bach
J F
JF
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002452:Cell Count; D003114:Colony-Forming Units Assay; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006412:Hematopoietic Stem Cells; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D013154:Spleen / Q000473:pathology
D016178:Granulocyte-Macrophage Colony-Stimulating Factor