Abstract
By means of a cytological technique involving 5-bromodeoxyuridine, acridine orange, and fluorescence microscopy, the asynchronously replicating, hence genetically inactivated, X chromosome was identified in 6-to 8-day embryos from female mice heterozygous for Searle's translocation T(X;16)16H (abbreviated as T16H) mated with either karyotypically normal males or males carrying Cattanach's translocation T(X;7)lCt in order to analyse the way in which the total inactivation of the normal X is achieved in adult T16H heterozygotes. Embryos examined included 9 Xn/X(7);16/16, 3X16/Xn;16x/16, 12X16/X(7);16x/16, 5 X16/Xn; 16/16, 8 X16/X(7); 16/16 and 2 Xn/Y; 16x/16/16. In these notations X16, 16x, X(7) and Xn represent Searle's X with the centromeric segment of the X, Searle's X with the centomeric segment of chromosome 16, Cattanachs's X with insertion of a chromosome 7 segment, and normal X, respectively. The X(7) exerted no apparent effect upon embryonic development up to the 8th day of gestation and X chromosome inactivation. — The asynchronously replicating X was the Xn in X16/ Xn;16x/16 and X(7) in X16/X(7);16x/16 embryos except a small number of cells on day 6 (13/493) and on day 7 (1/886) in which almost the entire 16x replicated asynchronously. The X16, on the other hand, never showed replication asynchrony. That the X16 is indeed unable to become inactivated was indicated by the observation that the X16 as well as Xn or X(7) did not replicate asynchronously in Xn/X16; 16/16 and X16/X(7); 16/16 embryos. X16-inactive cell lines, if occurring, should have been genetically less unbalanced than any other cell line in such embryos. It is highly likely therefore that the ultimate inactivation pattern in T16H heterozygotes has been accomplished by (1) the inability of the X16 to become inactive; (2) inactivation in favor of the Xn; and (3) rapid elimination of 16x-inactive cells. Severe growth retardation and early death of X16/Xn;16/16 and X16/X(7); 16/16 embryos having no inactive X suggested that functional X disorny is detrimental to embryogenesis. These embryos further indicated that the concurrence of at least two X chromosomal loci separated by the T16H breakpoint is necessary for the homologous X chromosome becoming inactivated.
Similar content being viewed by others
References
Cattanach, B.M.: A chemically-induced variegated-type position effect in the mouse. Z. Vererbungsl. 92, 165–182 (1961)
Cattanach, B.M.: Position effect variegation in the mouse. Genet Res. (Camb.) 23, 291–307 (1974)
Cattanach, B.M.: Control of chromosome inactivation. Annual Rev. Genet. 9, 1–18 (1975)
Cattanach, B.M., Isaacson, J. H.: Genetic control over the inactivation of autosomal genes attached to the X-chromosome. Z. Vererbungsl. 96, 313–323 (1965)
Distèche, C.M., Eicher, E.M., Latt, S.A.: Late replication in an X-autosome translocation in the mouse: Correlation with genetic inactivation and evidence for selective effects during embryogenesis. Proc. nat. Acad. Sci. (Wash.) 76, 5234–5238 (1979)
Eicher, E.M.: X-autosome translocations in the mouse: Total inactivation versus partial inactivation of the X-chromosome. Advanc. Genet. 15, 175–259 (1970)
Eicher, E.M., Nesbitt, M.N., Francke, U.: Cytological identification of the chromosomes involved in Searle's translocation and the location of the centromere in the X chromosome of the mouse. Genetics 71, 643–648 (1972)
Ford, C.E., Evans, E.P.: Non-expression of genome unbalance in haplophase and early diplophase of the mouse and incidence of karyotypic abnormality in post-implantation embryos. In: Chromosomal errors in relation to reproductive failure. (A. Boue and C. Thibault, eds.), pp. 271–285. Paris: I.N.S.E.R.M. 1973
Francke, U., Nesbitt, M.N.: Cattanach's translocation: Cytological characterization by quinacrine mustard staining. Proc. nat. Acad. Sci. (Wash.) 68, 2918–2920 (1971)
Hagemeijer, A., Hoovers, J., Smit, E.M.E., Bootsma, D.: Replication pattern of the X chromosome in three X/autosomal translocations. Cytogenet. Cell Genet. 18, 333–348 (1977)
Kouri, R.E., Miller, D.A., Miller, O.J., Dev, V.G., Grewal, H.S., Hutton, J.J.: Identification by quinacrine fluorescence of the chromosome carrying mouse linkage group I in the Cattanach translocation. Genetics 69, 129–132 (1971)
Leisti, J.T., Kaback, M.M., Rimoin, D.L.: Human X-autosome translocations: differential inactivation of the X chromosome in a kindred with an X-9 translocation. Amer. J. Hum. Genet. 27, 441–453 (1975)
Lyon, M.F.: Gene action in the X chromosome of the mouse (Mus musculus). Nature (Lond.) 190, 372–373 (1961)
Lyon, M.F.: Lack of evidence that inactivation of the mouse X-chromosome is incomplete. Genet. Res. (Camb.) 8, 197–203 (1966)
Lyon, M.F., Searle, A.G., Ford, C.E., Ohno, S.: A mouse translocation suppressing sex-linked variegation. Cytogenetics 3, 306–323 (1964)
Martin, G.R., Epstein, C.J., Travis, B., Tucker, G., Yatziv, S., Martin, D.W., Jr., Clift, S., Cohen, S.: X-chromosome inactivation during differentiation of female teratocarcinoma stem cells in vitro. Nature (Lond.) 271, 329–333 (1978)
Monk, M.: Biochemical studies on mammalian X chromosome activity. In: Development in mammals, vol. 3. (M.H. Johnson, ed.), pp. 189–223. Amsterdam: North Holland 1978
Monk, M., Harper, M.I.: Sequential X chromosome inactivation coupled with cellular differentiation in early mouse embryos. Nature (Lond.) 281, 311–313 (1979)
Nesbitt, M.N., Francke, U.: A system of nomenclature for band pattern of mouse chromosomes. Chromosoma (Berl.) 41, 145–158 (1975)
Ohno, S.: Conservation of ancient linkage groups in evolution and some insight into the genetic regulatory mechanism of X-inactivation. Cold Spr. Harb. Symp. quant. Biol. 38, 155–164 (1973)
Ohno, S., Lyon, M.F.: Cytological study of Searle's X-autosome translocation in Mus musculus. Chromosoma (Berl.) 16, 90–100 (1961)
Rattazzi, M.C., Cohen, M.M.: Further proof of genetic inactivation of the X chromosome in the female mule. Nature (Lond.) 237, 393–395 (1972)
Ray, M., Gee, P.A., Richardson, B.J., Hamerton, J.L.: G6PD expression and X chromosome late replication in fibroblast clones from a female mule. Nature (Lond.) 237, 396–397 (1972)
Russell, L.B.: Mammalian X-chromosome action: Inactivation limited in spread and in region of origin. Science 140, 976–978 (1963)
Russell, L.B.: Another look at the single-active-X-hypothesis. Trans. N. Y. Acad. Sci. 26, 726–736 (1964)
Russell, L.B., Bangham, J.W.: Variegated-type position effects in the mouse. Genetics 44, 532 (abstr.) (1959)
Russell, L.B., Cacheiro, N.L.A.: The use of mouse X-autosome translocations in the study of X-inactivation pathways and nonrandomness. In: Genetic mosaics and chimeras in mammals. (L.B. Russell, ed.), pp. 393–416. New York: Plenum Press 1978
Russell, L.B., Montgomery, C.S.: Comparative studies on X-autosome translocations in the mouse. I. Origin, viability, fertility and weight of five T(X;1)'s. Genetics 63, 103–120 (1969)
Russell, L.B., Montgomery, C.S.: Comparative studies on X-autosome translocation in the mouse. II. Inactivation of autosomal loci, segregation, and mapping of autosomal breakpoints in five T(X;1)'s. Genetics 64, 281–312 (1970)
Searle, A.G.: Is sex-linked Tabby really recessive in the mouse? Heredity 17, 297 (abstr.) (1962)
Takagi, N.: Preferential inactivation of the paternally derived X chromosome in mice. In: Genetic mosaics and chimeras in mammals. (L.B. Russell, ed.), pp. 341–359. New York: Plenum Press 1978
Takagi, N., Oshimura, M.: Fluorescence and Giemsa banding studies of the allocyclic X chromosome in embryonic and adult mouse cells. Exp. Cell Res. 78, 127–135 (1973)
Takagi, N., Sasaki, M.: Preferential inactivation of the paternally derived X chromosome in the extraembryonic membranes of the mouse. Nature (Lond.) 256, 640–642 (1975)
Takagi, N., Wake, N., Sasaki, M.: Cytologic evidence for preferential inactivation of the paternally derived X chromosome in XX mouse blastocysts. Cytogenet. Cell Genet. 20, 240–248 (1977)
Therman, E., Patau, K.: Abnormal X chromosomes in man: Origin, behavior and effects. Humangenetik 25, 1–16 (1974)
West, J.P., Frels, W.I., Chapman, V.M., Papaioannou, V.E.: Preferential expression of the maternally derived X chromosome in the mouse yolk sac. Cell 12, 873–882 (1977)
Wroblewska, J., Dyban, A.P.: Chromosome preparation from embryos during early organogenesis: dissociation after fixation, followed by air drying. Stain Technol. 44, 147–150 (1969)
Yoshida, M.C., Sasaki, M.: Euploid somatic recombinants with two active X or XY1Y2 chromosomes isolated from cultured male Indian muntjac cells after HVJ virus fusion, and their use for gene assignment. Somatic Cell Genet. 4, 437–450 (1978)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Takagi, N. Primary and secondary nonrandom X chromosome inactivation in early female mouse embryos carrying Searle's translocation T(X; 16)16H. Chromosoma 81, 439–459 (1980). https://doi.org/10.1007/BF00368155
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00368155