Alterations in growth, haematopoiesis and serum chemistry profiles infitness 1 ^4226SB mutant mice

Abstract

We investigated patterns of growth, haematopoiesis and alterations in serum chemistry profiles that were associated with anN-ethyl-N-nitrosourea-induced mutation in thefitness 1 locus in chromosome 7 in mice. Mice hemizygous for thefit 1 mutation [c fit 1 ^4226SB /Df(c Mod2 sh1) ^VT] had growth retardation characterised by decreased body weights, shorter body lengths and tail lengths at 40 and 60 days of age compared to normal homozygous control mice [c ^ch +/ c ^ch+]. Haemograms revealed that mice hemizygous for thefit 1 ^226SB mutation that were killed at 40 days had microcytic, hypochromic anaemia that was mildly regenerative in nature. No significant differences were detected in total leucocyte counts, differential leucocyte counts and platelet counts between hemizygous mutant mice and control mice. Haemograms from the surviving mice hemizygous for thefit 1 ^4226SB mutation that were killed at 60 days indicated that the haemoglobin concentrations, mean corpuscular volumes and mean corpuscular haemoglobin concentrations were significantly decreased compared to normal controls. The reticulocyte counts and the platelet counts from the mice hemizygous for thefit 1 ^4226SB mutation were mildly increased compared to normal controls killed at 60 days. Serum chemistry analyses at 40 days of age indicated that the hemizygousfit 1 mutant mice had hypoproteinaemia characterised by hypoalbuminaemia and hypoglobulinaemia. They also developed hypoglycaemia, mild hyperphosphataemia and moderate elevation in the activity of alkaline phosphatase in serum. Quantitative isozyme analysis indicated that the increase in total serum alkaline phosphatase activity in the hemizygous mutant mice was due to an increase in the bone isozyme. In addition to those alterations in the serum chemistry profile noted above, hemizygous mutant mice killed at 60 days had an extremely mild increase in urea nitrogen concentration and mildly increased activities of alanine aminotransferase and aspartate aminotransferase in serum. From these data, it was concluded that thefit 1 ^4226sb mutation m mice causes growth retardation, microcytic, hypochromic anaemia, and alterations in serum chemistry profiles that suggest lesions in one or more organ system(s). The exact mechanism(s) by which thefit 1 ^4226SB mutation mediates these lesions remains to be elucidated.