HEMATOPOIETIC STEM-CELL FUNCTION IN MOTHEATEN MICE

Abstract

Mice homozygous for the autosomal recessive mutation motheaten have normal numbers of multipotential hematopoietic stem cells in the bone marrow and spleen as determined by spleen colony assay. Histologic examination shows no qualitative abnormality in morphology of stem cell colonies in recipients of bone marrow or spleen cells from motheaten mice. Despite the apparently normal ontogeny, distribution and differentiative capacity of CFU stem cells, bone marrow and spleen cells from motheaten mice fail to save congenic +/+ lethally .gamma.-irradiated hosts. This impaired lifesparing capacity is not due to defective self-renewal but appears to be due in part to pulmonary hemorrhage from alveolar capillaries in the .gamma.-irradiated hosts. Treatment of motheaten mice with 500 R .gamma.- irradiation followed by reconstitution with normal bone marrow cells increases the lifespan of this mutant to 10 mo. of age. The early onset of pneumonitis and subsequent short lifespan of motheaten mice are determined at the level of progenitor cells in the bone marrow.