ALBERS-SCHONBERGS DISEASE (OSTEOPETROSIS) - FROM A DEVELOPMENTAL DISEASE OF BONE TO A PRE T-CELL LEUKEMIA SYNDROME INVOLVING A NEW RETROVIRUS - AN ILLUSTRATION OF THE INTEREST OF ANIMAL-MODELS

Nearly 70 years passed between Albers-Schonberg's initial roentgenographic description of osteopetrosis, or marble bone disease, in a patient and Donald Walker's first "cure" of the disease in a mutant mouse strain in 1973. Subsequently there has been a rapid development of knowledge about this rare and heterogeneous human disease. The first breakthrough in understanding osteopetrosis at the cell level is due to Walker's initial success in curing bone lesions in the microphthalmic (mi/mi) and grey-lethal (gl/gl) mice by parabiosis or normal bone marrow injection. This pioneering experiment led to reconsider osteopetrosis as a developmental disease due to deficient hematopoietic cells with osteolytic capabilities. The second advance in our understanding of the disease was the delineation of the specific factors which were responsible for the early death of a mutant osteopetrotic rat, strain (op/op). This work led us to reconsider osteopetrosis as an immune deficiency syndrome, curable by bone marrow injection. Another animal model taught that osteopetrosis and immunodepression could be induced by a retrovirus, the feline leukemia virus (FeLV). It was this model which led us to search for a retrovirus as the causal agent of human osteopetrosis and we were able to demonstrate the presence of such a virus in a patient suffering from the benign form of the disease and seronegative for HIV-1, HIV-2 and HTLV-1. Although no leukemia developed herein, contrarily to what happens in cats infected by FeLV, we observed in vitro, in long-term culture of the mononucleated blood cells isolated from that patient, the establishment of a T-cell line (OKT3+, OKT4+) able to produce the virus. These observations led us to reconsider osteopetrosis as a pre T-cell leukemia syndrome involving a retrovirus which seems different from the human retroviruses isolated until now.