Hertwig's anemia (gene symbol, an) is a single gene mutation on Chromosome 4 of the mouse that, when homozygous, causes a mild macrocytic anemia throughout life, severely reduces fertility, and predisposes aging mice to the development of histiocytic sarcoma (greater than 90% tumor incidence). Congenic mice differing only in the an/an gene region will be used to study particular aspects of an/an histiocytic sarcoma. Chromosome abnormalities have been observed in 5-15% of somatic cells from an/an mice. Abnormal cell division during hemopoietic maturation and subsequent loss of aneuploid cells could produce the anemia in an/an mice. Similarly, reduced fertility could be caused by germ cell death resulting from abnormal cell division. Preliminary work on an/an histiocytic sarcoma demonstrates that primary tumor cells (64-100%) are chromosomally abnormal. Primary tumors and transplanted tumors will be analyzed using G-banded karyotypes to define any common chromosome abnormality. Many mammalian cancers are associated with specific chromosomal changes and oncogenes. One oncogene, c-mos, is located on the same chromosome as the an gene. By examining DNA from congenic +/+ and an/an mice and DNA from histiocytic sarcomas it will be possible to determine whether c-mos has been rearranged or amplified in tumor cells. In addition, probes from other genes closely linked to the an gene will be used to determine if this gene region undergoes amplification or rearrangement in histiocytic sarcoma. The effect of genetic environment on histiocytic sarcoma development will be examined using two methods. Transplantation of an/an tumor cells into congenic young +/+ and an/an mice will be used to determine whether a normal cellular environment is less permissive of tumor growth than the an/an environment. Transplantation of bone marrow stem cells between +/+ and an/an mice will be used to determine whether bone marrow stem cells or their derivatives express the predisposition towards histiocytic sarcoma development in hosts with alternative genotype. Cellular markers such as surface antigens and enzymes will be defined for histiocytic sarcoma cells. This characterization will allow better classification of this tumor and comparisons of this tumor with others that occur in mouse and man.
| Barker, Jane E; Deveau, Susan A; Compton, Sheila T et al. (2005) High incidence, early onset of histiocytic sarcomas in mice with Hertwig's anemia. Exp Hematol 33:1118-29 |
| Eppig, J T; Barker, J E (1989) Deleterious effects of irradiation and bone marrow transplantation therapy in the genetically anemic an/an mouse. Blood 73:1373-9 |
