Radiographic, histologic, and cytologic lesions associated with mutations in the fitness1(4226SB) locus of mice.
OBJECTIVE
Previous investigation of fitness1(4226SB) mice revealed growth retardation and microcytic, hypochromic anemia with functional iron deficiency. Serum biochemical analysis suggested protein-losing enteropathy and liver dysfunction.


METHODS
Radiography was done to assess lumbar bone lesions in mice hemizygous for fitness1 (fit1) [c fit1(4226SB/Df(c Mod2 sh1)26DVT] and age-matched sibling controls [c(ch)+/c(ch)+] at 40 or 60 days of age. Macroscopic and microscopic lesions were evaluated at necropsy. Bone marrow was examined cytologically to evaluate hematopoietic lesions.


RESULTS
Mice hemizygous for fit1 had radiographically evident lumbar vertebral abnormalities, including various degrees of vertebral body fusion, with 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. Marked splenomegaly and mild cardiomegaly were evident, and bone marrow color ranged from normal to slightly pale. The spleen had marked extramedullary hematopoiesis; lumbar vertebrae contained microscopic lesions that corresponded to the radiographic lesions. Cytologic examination of bone marrow revealed normocellular to hypocellular status, with mild to moderate erythroid hypoplasia characterized by mild increase in the myeloid-to-erythroid cell ratio, decreased percentage of erythroid precursors, and slight increase in percentage of myeloid precursor cells.


CONCLUSIONS
Mutations in fit1 directly or indirectly cause alteration(s) in blood, organs of hematopoiesis (bone marrow, spleen, and liver), heart, and vertebral column, and suggest that this mouse may be a good model for study of scoliosis and relationships between iron metabolism and bone growth.
Department of Pathology, The University of Tennessee, Knoxville 37901-1071, USA.
A E
AE
Schultze
M F
MF
McEntee
G B
GB
Daniel
D K
DK
Johnson
D018798:Anemia, Iron-Deficiency / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D005260:Female; D000072179:Interleukin-1 Receptor-Like 1 Protein; D007501:Iron / Q000378:metabolism; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains / Q000235:genetics*; D017354:Point Mutation; D011247:Pregnancy; D011506:Proteins / Q000235:genetics*; D011859:Radiography; D018123:Receptors, Interleukin; D012600:Scoliosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology
C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008565:Membrane Proteins; D011506:Proteins; D018123:Receptors, Interleukin; D007501:Iron