Radiographic, histologic, and cytologic lesions associated with mutations in the Fitness1(4226SB) locus of mice

Background and Purpose: Previous investigation of fitness1(4226SB) mice rev ealed growth retardation and microcytic, hypochromic anemia with functional iron deficiency. Serum biochemical analysis suggested protein-losing enter opathy and liver dysfunction, Methods: Radiography was done to assess lumbar bone lesions in mice hemizyg ous for fitness1 (fit1) [c fit1(4226SB)/Df(c Mod2 sh1)(26DVT)] and age-matc hed sibling controls [C-ch+/c(ch)+] at 40 or 60 days of age. Macroscopic an d microscopic lesions were evaluated at necropsy, Bone marrow was examined cytologically to evaluate hematopoietic lesions. Results: Mice hemizygous for fit1 had radiographically evident lumbar verte bral abnormalities, including various degrees of vertebral body fusion, wit h loss of intervertebral disk spaces and mild, generalized osteopenia, All mutant mice had scoliosis, Several mutant mice had lordosis and/or kyphosis of variable severity and mild subluxation at the lumbosacral junction. Mar ked splenomegaly and mild cardiomegaly were evident, and bone marrow color ranged from normal to slightly pale. The spleen had marked extramedullary h ematopoiesis; lumbar vertebrae contained microscopic lesions that correspon ded to the radiographic Lesions. Cytologic examination of bone marrow revea led normocellular to hypocellular status, with mild to moderate erythroid h ypoplasia characterized by mild increase in the myeloid-to-erythroid cell r atio, decreased percentage of erythroid precursors, and slight increase in percentage of myeloid precursor cells. Conclusions: Mutations in fit1 directly or indirectly cause alteration(s) i n blood, organs of hematopoiesis (bone marrow spleen, and liver), heart, an d vertebral column, and suggest that this mouse may be a good model for stu dy of scoliosis and relationships between iron metabolism and bone growth.