Salome Gluecksohn-Waelsch

Lack of Association between ESR1 and CYP1A1 Gene Polymorphisms and Susceptibility to Uterine Leiomyoma in Female Patients of Iranian Descent

Uterine leiomyoma (UL) is the most common benign smooth muscle cell tumor with as yet unknown etiology and pathogenesis. This study was carried out to investigate the association of ESR1-351 A>G, ESR1 -397 T>C and CYP1A1 (Ile462Val) polymorphisms with UL in female patients of Iranian origin. In this case-control study, 276 patients with UL and 156 healthy women were recruited. The genetic polymorphisms ESR1-351 A>G, ESR1-397 T>C and CYP1A1 (Ile462Val) were genotyped by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). No significant difference were found in frequencies of both genotypes and alleles of ESR1-351 A>G, ESR1-397 T>C and CYP1A1 (Ile462Val) polymorphisms between the two groups (p>0.05). Our findings indicated that these ESR1 and CYP1A1 polymorphisms were not associated with the development of UL in the cases reported here.

LETHAL GENES AND ANALYSIS OF DIFFERENTIATION.

material of one atomic type can be made to diffuse to dislocations where it precipitates. The concentration of vacancies in the other atomic sublattice is therefore reduced along with a reduction in concentration of conduction electrons or holes in the semiconductor. The equilibrium concentration of holes in PbTe crystals as a function of precipitation temperature is shown in Fig. 6 (5). This method could in principle be pursued to very low charge carrier concentrations but is limited in practice by the increasingly long diffusion times required to reach equilibrium at lower temperatures.

The T-locus of the mouse: implications for mechanisms of development.

Publisher Summary This chapter presents a discussion of the various investigations of the T-locus in the hope of arriving at an integrated picture of present knowledge and of making this material accessible to further analysis with the help of present concepts and methods. A molecular study of the T-locus, with particular attention to ribosomal DNA, is suggested strongly by an apparent analogy of the t-mutants to the bobbed mutants in Drosophila. Certain attributes of the t-mutants, in particular, are reminiscent of those of bobbed mutants that have been interpreted as partial deficiencies of ribosomal DNA, and a partial deletion of the nucleolar organizer. Among the striking parallels between the two classes of mutants is, first of all, their liability as expressed in exceptionally high “mutation” rates. The mutant alleles of bobbed have been interpreted to be hypomorphs. When speculating about the possible significance of the T-locus in the mouse in processes of development and differentiation, the general problem of the relatively vast amount of DNA in the cells of higher organisms appears relevant. There has been renewed speculation about the great increase of DNA content as a possibly essential concomitant of increased complexity of organization. The chapter discusses two recent theories of gene regulation in higher cells that may be of relevance to the possible nature of this complex locus.

Fine structure of mutant (muscular dysgenesis) embryonic mouse muscle.

Abstract This investigation is concerned with the ultrastructure of embryonic muscle cells in mice homozygous for the mutation mdg (muscular dysgenesis). The earliest abnormalities are detected at a gestational age of 14 days when the sarcoplasmic reticulum of mutant cells begins to appear dilated. In later stages swollen sarcoplasmic reticulum is seen in all muscle cells as well as nuclear abnormalities and cell death. The correlation between the ultrastructural abnormalities of the sarcoplasmic reticulum and the other cellular abnormalities is discussed, as well as the possible relevance of the structural abnormalities to the total absence of muscle function in mutant homozygotes.

THE HEREDITARY TRANSMISSION OF HEMOGLOBIN DIFFERENCES IN MICE

The existence, in inbred strains of mice, of two different types of electrophoretic hemoglobin patterns has been demonstrated with the method of paper electrophoresis (1). Preliminary studies of the distribution of these different patterns in the inbred strains tested indicated strongly a genetic basis of hemoglobin differences in mice. It is the purpose of the present communication to report the results of breeding experiments designed to test the assumption of a hereditary transmission of these differences and to determine the mode of inheritance.

Multiple biochemical effects of a series of x-ray induced mutations at the albino locus in the mouse.

Further studies of the four radiation-induced lethal albino mutations causing glucose 6-phosphatase deficiency in the mouse have shown that there is also a deficiency of tyrosine aminotransferase in the newborn albino mutants. These two enzymes can be induced in fetal and newborn heterozygous or homozygous normal littermate controls by injection of glucagon or dibutyryl cyclic AMP, but not in the albino mutants. Microsomal NADH-cytochrome c reductase was found to be increased in the albino mutants. The multiple biochemical abnormalities in the albino mutants, in addition to the lack of gene dosage effect in the heterozygotes, suggest the involvement of genes other than the structural genes for particular enzymes. When a new radiation-induced lethal albino mutation was tested against the four original alleles, complementation resulted, and double heterozygotes were found to be viable, with normal enzyme levels.

Regulatory genes in development

Abstract At present, only a limited number of regulatory genes acting during development of higher eukaryotes have been described. The identification of such regulatory genes and the analysis of their mode of action depend largely on the availability of suitable model systems, some of which are described in this review.

Development in organ tissue culture of kidney rudiments from mutant mouse embryos

The developmental potencies of components of the kidney rudiment of prospectively kidneyless mice, homozygous for the Sd mutation, were studied in organ tissue culture. Intact kidney rudiments of Sd homozygous embryos were able to undergo differentiation in vitro, although to a lesser degree than normal and with abnormalities of the ureter and reduced mesenchymal tubule formation. Reciprocal combinations of normal and mutant kidney mesenchyme with normal and mutant ureter resulted in differentiation of ureteric branches and tubule formation. Normal as well as mutant spinal cord elicited tubule differentiation in normal or mutant kidney mesenchyme. Whereas the Sd mutation does not affect differentiation potentials of the embryonic kidney rudiment qualitatively, a smaller proportion of mutant than of normal rudiments shows differentiation, and those rudiments which do differentiate start later and produce fewer tubules than normal. The possible mechanisms underlying this effect of the genetic change on kidney differentiation are discussed.

Developmental genetics of a recessive allele at the complex T-locus in the mouse

Abstract The lethal alleles t4 and t9 at the T-locus on chromosome IX of the house mouse arose independently in a balanced lethal tailless line. Since they did not show complementation and were found to be indistinguishable genetically as well as in their developmental effects, they are considered to be identical. Mutant homozygous embryos can be recognized histologically soon after implantation, i.e., 6 days after fertilization, and they die between 8 and 9 1 2 days. The abnormal embryos are characterized by over-development and duplications of neural structures in contrast to deficiencies of differentiation of normal mesodermal elements, such as somites. The mutation seems to interfere with normal regulation of the pattern of embryonic differentiation. The disturbance of differentiation is discussed in its potential significance for the analysis of mechanisms of embryonic regulation and genetic control of differentiation in higher organisms.

Glucose 6-phosphatase deficiency, mechanisms of genetic control and biochemistry.

Mechanisms are discussed by which several radiation-induced lethal mutations in the mouse control enzyme activity and morphogenesis. These mutations behave as alleles at the albino locus in chromosome I; furthermore, all of them suppress glucose 6-phosphatase activity, resulting in perinatal death of albino homozygotes. Additional pleiotropic effects, and the absence of a dosage effect in heterozygotes, are not easily explained by a mutational change in the structural gene for glucose 6-phosphatase. The mutations might affect membrane proteins and thus render membrane structure abnormal; such membranes may lack the ability to bind tyrosinase as well as glucose 6-phosphatase and may also be responsible for morphogenetic abnormalities.