Effect of Alleles W~v and W~y of the Dominant White Spotting Mutation on the Preimplantation Development of Mice

摘要

Studies of cell interactions in early embiyogenesis of mammals are important for understanding the characteristic features of mammalian ontogeny, because early cell divisions determine which blastomers will give the cells that later will form the bodyof adult animal [1]. Cell interactions play a key role in morphoge-netic events that takes place during cell divisions [2]. According to modern ideas, there are two main forms of such interactions: ligand-receptor and permeable junction-mediated interactions [3].Gap junctions are formed only in eight-cell embryos; at earlier developmental stages, blastomers may contact via ligand— receptor interactions. The viability of embiyos is regulated by growth factors, the effect of which is realized predominantly through the receptors of the tyrosine kinase type [4]. The group of these receptors includes, in particular; the c-kit membrane receptors [5]. It is known that the dominant spotting mutation (W) in mice disturbs the structure of the c-kit gene, located in chromosome 5 [6]. This mutation affects the color of fur, erythropoiesis, and gametogenesis [7]. Locus W, in which the c-kit gene is located [6], is characterized by a strikingly high frequency of dominant mutations Currently, over 40 mutant alleles are known, the majority of which aie lethal in homozygous state [8]. In viable heterozygous animals, mutations disturb c-kit-ligand signal transmission as a result of decrease in the number of functional c-kit receptors on cell surface [8]. A similar mutation (KIT) occurs in the human [9]. Studies of the role of c-kit receptor tyrosine kinase in the ontogeny of mammals showed that c-kit transcripts affect oocyte maturation [4,10]. Receptor tyrosine kinases play a key role in fertilization and triggerthe multistage mechanism of activation during the interaction between the egg and spermatozoid. It was shown that the truncated form of c-kit kinase, which is expressed during spermi-ogenesis, is involved in the activation of the egg by the sperm [10]. It was also reported that, in early mouse embryos, the expression of the c-kit gene is not detected until the eight-cell stage [11]. Other studies showed that, after fertilization, the expression of c-kit mRNA stops; it starts again only at the late two-cell stage and continues at a low level over the entire preimplantation development. In early embryos, the ligand of c-kit receptor is not transcribed; however, the ligand transcription was detected in cumulus cells, oviducts, and the uterus [12]. The role of c-kit-ligand system can be determined in the studies of the effect of mutations in the W locus on early embiyogenesis of mice.