Karl Fredga

Cytological identification of two X-chromosome types in the wood lemming (Myopus schisticolor)

In the wood lemming (Myopus schisticolor) three genetic types of sex chromosome constitution in females are postulated: XX, X*X and X*Y (X*=X with a mutation inactivating the male determining effect of the Y chromosome). Males are all XY. It is shown in the present paper that the two types of X chromosomes, X and X*, exhibit differences in the G-band patterns of their short arms. In addition, it was demonstrated in unbanded chromosomes that the short arm in X* is shorter than in X. The origin of these differences is still obscure; but they allow to identify and to distinguish the individual types of sex chromosome constitution, as of XX versus X*X females and of X*Y females versus XY males, on the basis of G-banded chromosome preparations from somatic cells.

X-linked genes of the H-Y antigen system in the wood lemming (Myopus schisticolor)

SummaryH-Y antigen was investigated in 18 specimens representing six different sex chromosome constitutions of the wood lemming (Myopus schisticolor). The control range of H-Y antigen was defined by the sex difference between normal XX females (H-Y negativeper definitionem) and normal XY males (H-Y positive, full titer). H-Y antigen titers of the X*Y and X*0 females were in the male control range, while in the X*X and X0 females the titers were intermediary. Data were obtained with two different H-Y antigen assays: the Raji cell cytotoxicity test and the peroxidase-antiperoxidase (PAP) method. Fibroblasts, gonadal cells, and spleen cells were checked. Presence of full titers of H-Y antigen in the absence of testis differentiation is readily explained by the assumption of a deficiency of the gonadspecific receptor of H-Y antigen. Since sex reversal is inherited as an X-linked trait, genes for this receptor are most likely X-linked. The implications of our findings are discussed in connection with earlier findings concerning H-Y antigen in XY gonadal dysgenesis in man and the X0 situation in man and mouse.

Sex-chromosome aberrations in wood lemmings (Myopus schisticolor)

The wood lemming displays certain peculiar features: (1) The sex ratio shows a prevalence of females (FRANK, 1966; KALELA and OKSALA, 1966), and some females produce only female offspring (KALELA and OKSALA, 1966). (2) In a considerable proportion (in the present material, slightly less than half) of the females, an XY chromosome complement is found in the somatic tissues, but the Y is absent in the germ line of those studied (Fredga et al., 1976). Therefore, (3) a mechanism of double nondisjunction in early fetal life of XY females has to be postulated, which replaces the Y in the germ line by duplication of the X. It is assumed (4) that the X of XY females bears a sex-reversal factor that affects the male determining action of the Y (Fredga et al., 1977). There is (5) a strong presumption that in most cases the XY females are those that produce daughters only, but (6) a few exceptions may occur (FRANK, unpublished observations), suggesting that the regulation according to assumption 3 (perhaps also to 4) is incomplete in XY females. In the present report, four females are described with a 31,XO karyotype, two females with 33,XYY or 32,XY/33,XYY, respectively, two males with a 33,XXY, and one male with a 32,XX/33,XXY karyotype, as observed in a consecutive series of 502 wood lemmings. The incidence of sex-chromosome anomalies in liveborn and adult animals was 2.3%; the overall incidence, including embryos, was 1.79%. Neither the somatic XO constitution nor the existence of an extra Y in females precludes fertility. However, the XXY condition in the male results in sterility. There is certain evidence that an instability of the proposed mechanism for double mitotic nondisjunction of the sex chromosomes in oogonia accounts for the high rate of sex-chromosome aberrations in wood lemmings, at least when the mother is XY.

Sex determination and phenotype in wood lemmings with XXY and related karyotypic anomalies.

SummaryThe wood lemming, Myopus schisticolor, possesses a unique sex determining system comprising both XX and XY females. Normal female development in the presence of XY is guaranteed by a mutation on the X, apparently associated with a structural rearrangement in Xp. This mutation inactivates the testis-inducing and male-determining factor on the Y and distinguishes X* from X, and X*Y females from XY males. Normal fertility of X*Y females is ensured by a mitotic (double) nondisjunction mechanism which, at an early fetal stage, eliminates the Y from the germ line and replaces it by a copy of the X*.Numerical sex chromosome aberrations are not infrequent and the trisomics XXY and X*XY are relatively common. XXY individuals are sterile males with severe suppression of spermatogenesis. Among X*XY animals, both males and females, as well as a true lateral hermaphrodite have been observed. Primary deficiency of germ cells, impairment of spermatogenesis and sterility are characteristic traits of the X*XY males, whereas X*XY females have normal oogenesis and are fertile. Both these extremes (except female fertility) coexist in the true hermaphrodite described in the present study. These apparently contradictory observations are explainable under the assumption that X* and X in X*XY individuals are inactivated non-randomly or that the cells are distributed unequally. Inactivation of the X or X* determines whether or not the H-Y antigen will be expressed. When comparing conditions in Myopus and in man, an additional assumption has to be made in relation to the gene(s) involved in sex determination, located in Xp:In Myopus they do not escape inactivation, whereas in man they have been claimed to remain active.

Idiogram and trisomy of the water vole (Arvicola terrestris L.), a favourable animal for cytogenetic research

The chromosomes of the water vole (Arvicola terrestris L.) were investigated in 2 female and 5 male animals from three different parts of Sweden. The somatic chromosomes were studied in direct preparations of cornea and bone marrow and in tissue cultures of testis, lung and heart. Meiosis was studied in one male. The chromosome number was 2n=36. No differences in regard to chromosome number and morphology were found among the seven control animals studied. Different chromosome types are represented and the karyotype of the species is favourable for chromosome studies. — An idiogram of the water vole was constructed from measurements of complete chromosome sets from ten heart cells. — In addition to the above normal material one young water vole, trapped in nature, was found to have 37 chromosomes and was trisomic for the smallest autosome. This autosome had a secondary constriction and took part in “satellite associations”. The cytologic similarities to Downs syndrome in man are striking and it is hoped that the water vole will become a valuable laboratory mammal, especially for elucidation of the chromosomal mechanisms of non-disjunction. The trisomic water vole had no obvious phenotypic abnormalities, but at least one feature was not within normal limits — its tail was unusually short. Also, the development of certain teeth was somewhat aberrant. Whether short tail and dental deformities are symptoms correlated with trisomy for the smallest autosome in the water vole is an open question so far.