CHLORAMBUCIL-INDUCED MUTATIONS IN MICE RECOVERED IN HOMOZYGOTES

Chlorambucil induced a number of recessive visible mutations in the mo use. Induction of these mutations was studied in two mating schemes, e ach designed to recover mutations after two intercrosses. In scheme 1, 10 mutations were detected in 82 mice; in scheme 2, 1 mutation was de tected in 19 mice. We have estimated that the proportion of gametes ca rrying a recessive visible mutation may be as high as 25% after a dose of 10 mg of chlorambucil per kg to early spermatids. Seven of these m utations caused morphologically distinct abnormalities, including (i) a cerebellar abnormality similar to that expressed in homozygotes for the reeler (rl) mutation; (ii) open eyelids at birth; (iii) a rostral head hemangioma; (iv) abnormally small spleens, anemia, and umbilical hemorrhages; (v) immobility at birth; (vi) polycystic kidneys; and (vi i) a circling behavior. Four additional mutations resulted in growth r etardation and a runting syndrome. Because, in earlier studies, all mo lecularly characterized mutations induced by chlorambucil in poststem cells have proved to be deletions, these recessive visible mutations a re probably deletions as well. These mutations may be useful in isolat ing and characterizing the genes responsible for the observed phenotyp es.