An inherited disease of the bone marrow identical in its pathophysiology to human hereditary spherocytosis has been described in the deer mouse, Peromyscus maniculatus. As Peromyscus are not inbred and of distinct individually-specific histocompatibility, they provide an experimental model system for the use of hemopoietic allotransplantation in the treatment of hereditary diseases of the erythron. Ninety adult mice were exposed to otherwise 100 per cent lethal doses of x-rays and then inoculated intravenously with 20 to 60 million nucleated marrow cells. Marrow was transplanted on a one-to-one donor recipient basis in four combinations of phenotypes: normal to normal; spherocytic to normal; spherocytic to spherocytic; and normal to spherocytic. Mortality and pathology were similar in all groups. Thirty per cent of the hosts died as a direct result of the irradiation within 20 days. Another 30 per cent subsequently succumbed to secondary disease presumably of graft-against-host origin, bringing the overall mortality to 60 per cent at the end of 10 weeks. At 3 months, however, the hematologic status of the survivors, nearly without exception, was of donor phenotype: Genetically spherocytic recipients of normal marrow contained normal red cells; conversely, wild type recipients of spherocytic marrow had assumed the mutant phenotype. Evidence of chronic grafthost interaction was obtained. By 7 months, six mice in the spherocytic to normal transplant group had reassumed the host hematologic phenotype, but only one animal in the normal to spherocytic group reverted to the mutant phenotype.
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