EXCEPTIONAL INHERITANCE OF A SEX-LINKED GENE IN THE MOUSE EXPLAINED ON THE BASIS THAT THE X/O SEX-CHROMOSOME CONSTITUTION IS FEMALE

Abstract

Until recent years, no sex-linked genes were known in the mouse. Thus, the tools for the genetic exploration of sex determining mechanisms were lacking. A sex-linked mutation, scurfy, discovered at this laboratory in 1949 has, on occasions , shown unexpected inheritance. In spite of the lethal effects of the mutation , it has been possible to carry out genetic analysis of the exceptional individuals (scurfy females) by means of ovarian transplantation. As a result, the array of possible explanations for the exceptional individuals could be narrowed down. Several alternative hypotheses, however, remained, with no decision possible between them. In the meantime, other sex-linked genes and adequate cytological techniques became available, and recent findings by Welshons and Russell' have shed much light on the sex-determining mechanism of the mouse. The present paper will describe our older work on the genetic analysis of the scurfy exceptions and show that the results are quite consistent with the proof, presented in the accompanying paper,' that X/O is female. Material and Methods.-The mutation scurfy, sf, occurred spontaneously in our MR-stock, a stock which was then in the process of being made homozygous for 7 standard recessives, most of them coat colors. Details concerning the phenotypic expression, derivation, and transmission of sf will be published elsewhere. Scurfy is inherited as a sex-linked recessive gene. Hemizygous males are characterized by a number of features. The external characteristics are: scaliness, first of the tail and later of other parts of the body; "tight" skin; and late opening of the eyelids. The condition is first recognizable externally at about 11 days of age by a reddening of the genital papilla. About two-thirds of the affected males die before weaning age, most of the remaining ones shortly after weaning. Occasional males have lived several months, one as long as six months, but all of these are runty and none has been fertile. Thus, the stock must be maintained by mating X81/X+ females with X+/Y males. Consequently, females with the scurfy phenotype were not expected to occur. Early in 1950, the first exceptional, scurfy, female was observed in the stock and a total of 29 have been obtained to date. (Frequency will be discussed below.) These exceptional females were phenotypically similar to Xsf/ Y males. Since they were presumably destined to die without reproducing, it was necessary to resort to ovarian transplantation in order to carry out genetic analysis, and ovaries from the first 13 cases that occurred were transplanted, mostly during the years 1950-1951. The fact that scurfy females do, indeed, die without reproducing was confirmed by the next 15 cases, which were not operated upon and died aged 16-45 days. Ovaries from the 29th scurfy female to be observed were transplanted in 1958. It is, of course, desirable to have genetic markers such that offspring of transplanted ovaries can be distinguished from offspring of regenerated host ovaries.2 554