Treatment of Hereditary Spherocytosis in Peromyscus by Radiation and Allogeneic Bone Marrow Transplantation

An inherited disease of the bone marrow identical in its pathophysiologyto 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 100per cent lethal doses of x-rays and then inoculated intravenously with 20 to60 million nucleated marrow cells. Marrow was transplanted on a one-to-onedonor 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 hostsdied as a direct result of the irradiation within 20 days. Another 30 per centsubsequently succumbed to secondary disease presumably of graft-against-hostorigin, bringing the overall mortality to 60 per cent at the end of 10 weeks. At3 months, however, the hematologic status of the survivors, nearly withoutexception, was of donor phenotype: Genetically spherocytic recipients of normalmarrow 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 spherocyticto normal transplant group had reassumed the host hematologic phenotype, but only one animal in the normal to spherocytic group reverted to themutant phenotype.

Submitted on May 24, 1966 Accepted on July 18, 1966