Barker J E, McFarland-Starr E C
Jackson Laboratory, Bar Harbor, ME 04609.
Blood. 1989 May 15;73(7):2014-7.
Mice with hemolytic anemia, sphha/sphha, have extremely fragile RBCs with a lifespan of approximately one day. Neither splenectomy nor simple transplantation of normal marrow after lethal irradiation cures the anemia but instead causes rapid deterioration and death of the mutant unless additional prophylactic procedures are used. In this report, we show that normal marrow transplantation preceded by sublethal irradiation increases but does not normalize RBC count. The mutant RBCs but not all the WBCs are replaced by donor cells. Splenectomy of the improved recipient causes a dramatic decrease in RBC count, indicating that the mutant spleen is a site of donor-origin erythropoiesis as well as of RBC destruction. Injections of iron dextran did not improve RBC counts. Transplantation of primary recipient marrow cells into a secondary host with a heritable stem cell deficiency (W/Wv) corrects the defect caused by residence of the normal cells in the sphha/sphha host. The original +/+ donor cells replace the RBCs of the secondary host, and the RBC count is normalized. Results indicate that the environment in the sphha/sphha host is detrimental to normal (as well as mutant) erythroid cells but the restriction is not transmitted.
患有溶血性贫血的sphha/sphha小鼠具有极其脆弱的红细胞，其寿命约为一天。脾切除或在致死性照射后单纯移植正常骨髓均无法治愈贫血，反而会导致突变体迅速恶化并死亡，除非采取额外的预防措施。在本报告中，我们表明在亚致死性照射后进行正常骨髓移植可增加红细胞计数，但无法使其恢复正常。供体细胞取代了突变的红细胞，但并非所有白细胞。对病情改善的受体进行脾切除会导致红细胞计数急剧下降，这表明突变的脾脏是供体来源的红细胞生成以及红细胞破坏的场所。注射右旋糖酐铁并未改善红细胞计数。将原受体骨髓细胞移植到具有遗传性干细胞缺陷（W/Wv）的二级宿主中，可纠正正常细胞在sphha/sphha宿主中停留所导致的缺陷。原来的+/+供体细胞取代了二级宿主的红细胞，红细胞计数恢复正常。结果表明，sphha/sphha宿主中的环境对正常（以及突变）红系细胞有害，但这种限制不会遗传。
