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Biomedical subjects

V M Chapman

Publications and source records attributed to V M Chapman.

133 records · Page 8Linked to original sources

A new H-2-linked class I gene whose expression depends on a maternally inherited factor.

The maternally transmitted antigen (Mta) is expressed on the cells of most strains of mice. It is a medial histocompatibility antigen, that is, it is recognized by unrestricted cytotoxic T lymphocytes as are major H antigens, but unlike these it is a weak transplantation antigen and does not itself restrict the T-cell recognition of minor H antigens. All other medial H antigens are encoded by genes closely linked to the major histocompatibility complex, H-2 in the mouse. By contrast, Mta appeared to follow extrachromosomal, maternal inheritance. Several substrains of NZB, NZO and non-inbred European NMRI mice are Mta-negative. Females of these strains bear only Mta- offspring, while females of the inbred Mta+ strains bear only Mta+ offspring. Repeated backcrossing from Mta+ females to NZB or NMRI males has shown that, given the right cytoplasmic genes, the chromosomal genes of these Mta- strains permit expression of Mta2. As the Mta type of a mouse cannot be influenced by embryo transfer or foster nursing, we concluded that it was determined by a cytoplasmic factor (Mtf), transmitted through the egg. We now show that a gene, Hmt, closely linked to the H-2 complex, is also required for expression of Mta.

Alleles↗

Differential expression of alpha-fetoprotein genes on the inactive X chromosome in extraembryonic and somatic tissues of a transgenic mouse line.

During development of the female mouse embryo, one of the two X chromosomes is inactivated in a random manner in most cell lineages. However, in the extraembryonic trophectoderm and primary endoderm lineages there is preferential inactivation of the paternally derived X chromosome. The inactivated X chromosomes of the extraembryonic and somatic tissues appear equally inactive at the level of the expression of X-linked genes. However, there are differences in the timing of their replication and the extent of DNA modification as determined by gene transfer. The identification of transgenic animals carrying X-linked modified alpha-fetoprotein (AFP) genes allowed us to examine whether the inactivation process extends to an autosomal gene which is normally expressed at high levels in specific extraembryonic and somatic cells, and if so, whether the inactivation process is different in these two tissues. Our results demonstrate that the X-linked AFP genes were expressed on the inactive X chromosome in the visceral endoderm of the yolk sac but not in fetal liver. Thus, the transcriptional activity of the AFP minigene on the inactive X chromosome is dependent on the tissue in which it resides, and most probably reflects differences in the nature of the maintenance of the inactive state of the extraembryonic and embryonic X chromosomes.

Animals↗

Mus musculus x Mus caroli hybrids: mouse mules.

Analysis of six enzymes using starch gel electrophoresis indicates that autosomal and X-linked genes of both parental species are expressed normally in M. musculus X M. caroli hybrids. There is no evidence for allelic repression for the four autosomally inherited enzymes. Banding patterns for G6PD and PGK-1 indicate that X-chromosome inactivation occurs and that the maternally derived M. musculus X-chromosome is preferentially expressed in the yolk sac. Despite normal genetic expression none of the four adult female hybrids was fertile and the male hybrids tended to be retarded during fetal development. The routine production of fetal M. musculus X M. caroli hybrids, heterozygous for three X-linked genes coding for G6PD, PGK-1, and HPRT, should provide an excellent system for the analysis of X-chromosome expression and an alternative to the mule for studies of hybrid reproduction and development.

Animals↗