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T Magnuson

Publications and source records attributed to T Magnuson.

85 records · Page 5Linked to original sources
PubMed1985

The early lethality of autosomal monosomy in the mouse.

Using male mice doubly heterozygous for pairs of Robertsonian translocation chromosomes that have one arm in common, mouse embryos monosomic for 11 of the 19 autosomes have been generated. All of these monosomies result in death prior to or during the implantation period, with only rare survivors being detected 6 days after fertilization. For some of the monosomies the onset of lethality can be detected during the third or fourth day of development, but others do not begin to die until sometime after the late blastocyst stage on day 4. Retardation of development, as revealed by decreased cell numbers, is often detectable prior to or after the onset of the lethal period. The period during which death occurs may spread over several days and does not coincide with any of the developmental landmarks of the pre- or peri-implantation period. Genetic factors that may affect the rate of cellular proliferation or other aspects of embryonic development appear to play an important role in determining exactly when individual monosomies result in death. The universal early lethality of the autosomal monosomies leads to the conclusion that a large number of loci scattered over all of the autosomes are involved in processes that are so concentration dependent that a 50% reduction is sufficient to produce very serious consequences.

Aneuploidy↗
PubMed1984

Oligosyndactyly: a lethal mutation in the mouse that results in mitotic arrest very early in development.

The mutation, oligosyndactyly, results in syndactyly, muscle anomalies, and diabetes insipidus in heterozygous mice. When homozygous, the mutation is lethal early in development. Although homozygous embryos are able to form blastocyst outgrowths (the in vitro equivalent to implantation), cells begin to accumulate in mitosis as early as the blastocyst stage. Even though the cytologic appearance is that of mitotic cells treated with a microtubule inhibitor such as colcemid, the homozygous embryos do, in fact, have normal appearing mitotic spindles. These results define the Os mutation as one which, in the homozygous state, prevents the movement of chromosomes from the metaphase plate. It is the first mammalian developmental mutation to be so defined and is unique among all mitotic arrest mutations thus far described in higher eucaryotes.

Animals↗
PubMed1982

Genetic control of early mammalian development.

A large body of evidence, derived by the use of genetic variants and deleterious mutations, indicates that the mouse embryo both expresses and requires expression of the embryonic genome during the two-cell stage of development, at or shortly after the time of onset of RNA synthesis. It seems hopeful that the study of these very early stages of embryonic development will not only provide us with information about the genetic control of the developmental events occurring shortly after fertilization but, because of the nature of the mutations that are expressed in the homozygous form during this period, will tell us much about the genetic control of later stages of morphogenesis and about the mechanisms by which chromosome imbalance states produce their deleterious effects.

Animals↗
PubMed1982

The development of monosomy 19 mouse embryos.

In general, autosomal monosomy is lethal much earlier in mammalian development than autosomal trisomy. In an attempt to understand why monosomy is so deleterious, we have begun to characterize the development of mouse embryos monosomic for chromosome 19. A dramatic loss of monosomy 19 embryos was found to occur between days 3 and 4 of development. This loss occurred both in vivo and in vitro and with intact blastocysts or isolated inner cell masses. Experiments with inbred strains showed that this loss was not due to the expression of recessive lethal genes. While monosomic embryos were found to have fewer cells than normal and trisomic litter-mates beginning at the early morula stage, the ability to form blastocysts is not interfered with. Electron microscopy revealed no difference in the cellular ultrastructure of monosomic when compared with diploid embryos. Furthermore, two-dimensional gel electrophoresis did not reveal any differences in the proteins synthesized by monosomic, trisomic or diploid litter-mates when examined at day 3 of development. These results indicate a lack of gross genomic disturbances in monosomic embryos. When monosomy in equilibrium diploid chimaeras were made, viable monosomic cells were found in day-9 post-implantation embryos, well past the lethal period. Thus, in chimaeric embryos, the normal cells appear to be able to provide whatever is lacking, suggesting that monosomy 19 is not a cell lethal. Instead, death may be due to a dosage alteration in specific gene products needed during early development.

Aneuploidy↗