ALTERATIONS IN GROWTH, HEMATOPOIESIS AND SERUM CHEMISTRY PROFILES IN FITNESS 1(4226SB) MUTANT MICE

We investigated patterns of growth, haematopoiesis and alterations in serum chemistry profiles that were associated with an N-ethyl-N-nitros ourea-induced mutation in the fitness I locus in chromosome 7 in mice. Mice hemizygous for the fit 1 mutation [c fit 1(4226SB)/Df(c Mod2 sh1 )(26DVT)] had growth retardation characterised by decreased body weigh ts, shorter body lengths and tail lengths at 40 and 60 days of age com pared to normal homozygous control, mice [c(ch)+/c(ch)+]. Haemograms r evealed that mice hemizygous for the fit 1(4226SB) mutation that were killed 40 days had microcytic, hypochromic anaemia that was mildly reg enerative in nature. No significant differences were detected in total leucocyte counts, differential leucocyte counts and platelets counts between hemizygous mutant mice and control mice. Haemograms from the s urviving mice hemizygous for the fit 1(4226SB) mutation that were kill ed at 60 days indicated that the haemoglobin concentrations, mean corp uscular volumes and mean corpuscular haemoglobin concentrations were s ignificantly decreased compared to normal controls. The reticulocyte c ounts and the platelet counts from the mice hemizygous for the fit 1(4 226SB) mutation were mildly increased were compared to normal controls killed at 60 days. Serum chemistry analyses at 40 days of age indicat ed that the hemizygous fit I mutant mice had hypoproteinaemia characte rised by hypoalbuminaemia and hypoglobulinaemia. They also developed h ypoglycaemia, mild hyperphosphataemia and moderate elevation in the ac tivity of alkaline phosphatase in serum. Quantitative isozyme analysis indicated that the increase in total serum alkaline phosphatase activ ity in the hemizygous mutant mice was due to an increase in the bone i sozyme. In addition to those alterations in the serum chemistry profil e noted above, hemizygous mutant mice killed at 60 days had an extreme ly mild increase in urea nitrogen concentration and mildly increased a ctivities of alanine aminotransferase and aspartate aminotransferase i n serum. From these data, it was concluded that the fit 1(4226SB) muta tion in mice causes growth retardation, microcytic, hypochromic anaemi a, and alterations in serum chemistry profiles that suggest lesions in one or more organ systems. The exact mechanism(s) by which the fit 1( 4226SB) mutation mediates these lesions remains to be elucidated.