Inherited histocompatibility changes in progeny of irradiated and unirradiated inbred mice

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Abstract
(1) F1-hybrid mice derived from a cross of the highly inbred strains: C57BL/6 and BALB/c, were tested for inherited changes of histocompatibility by an orthotopic inter-exchange of tail-skin grafts. The fathers of tested mice received either 522 rads of gonadal X-irradiation, or received no irradiation 2 months prior to mating.(2) Thirty-two mice with altered histocompatibilities were found in a total of 2572 complete tests. All of those mutant mice (twenty-one) that produced an adequate number of offspring were shown to pass the incompatibility on to their progeny.(3) Mutants were classified as to whether they effected a gain, a loss or both a gain and a loss in antigen specificity as determined by whether they rejected skin of donor mice or their skin was rejected by host mice. Twenty-six were clearly of the gain type, five were most likely gain type and only one showed both a loss and a gain effect. There was no clearcut evidence that loss types had occurred. The preponderance of gain types was tentatively explained as an artifact of the system used for the assay.(4) Several of the detected mutants were probably from parents carrying mutations that originated in past generations, for some mutant mice occurred in clusters.(5) There was no apparent effect of paternal irradiation (522 rads) on mutation frequency. The induced mutation rate was estimated to be less than 2·6 × 10−5/ gamete/rad.(6) Independent data on isografts from F1hybrids of proven non-carrier pedigreed parents provided an estimate of spontaneous mutation rate of 6·75 × 10−3/ gamete.(7) The estimate of doubling dose (greater than 260 rads) was consistent with the estimates for recessive lethals and visibles in mice.