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PubMed1994

The rapid degradation of mutant SecA protein in the Bacillus subtilis secA341 (ts) mutant causes a protein translocation defect in the cell.

To study the function of SecA protein and the protein translocation system of Bacillus subtilis, wild-type and mutant SecA proteins were characterized in vivo and in vitro. SecA protein was abundant in a wild-type strain (168) and existed in a stable homodimer. In contrast to this, SecA341 (ts) protein having an amino acid replacement from proline to leucine at residue 431 was undetectable by immunoblotting in the cell lysate of a secA341 mutant (TB301) at the nonpermissive temperature, 42 degrees C. Pulse-chase studies using 35S-methionine showed that newly synthesized SecA protein was rapidly degraded in the mutant at 42 degrees C. Purified SecA341 protein was more sensitive to trypsin and subtilisin than purified wild-type SecA protein in the presence of ATP. These results indicate that the secA341 mutation causes the rapid degradation of mutant SecA protein and a concomitant protein translocation defect in the cell.

Adenosine Triphosphatases↗

PubMed1994

Construction of Pta-Ack pathway deletion mutants of Escherichia coli and characteristic growth profiles of the mutants in a rich medium.

Escherichia coli grown in a rich medium excreted acetate and reused the acetate. Using cloned genes and a plasmid with a temperature-sensitive replication origin, three kinds of Pta-Ack pathway deletion mutants were constructed. Acetate production and reuse by wild-type cells grown in the rich medium was confirmed to largely occur through the Pta-Ack pathway. The deletion mutants of the gene encoding phosphotransacetylase secreted pyruvate before the secretion of acetate into the medium. A deletion mutant of the gene encoding acetate kinase grew at a slow rate, but its secretion and use of acetate were rapid. These results indicated that a pathway(s), other than the Pta-Ack pathway, functions in the control of excess carbon flow in the mutants.

Acetate Kinase↗

PubMed2006

Sucrase-isomaltase gene expression is inhibited by mutant hepatocyte nuclear factor (HNF)-1alpha and mutant HNF-1beta in Caco-2 cells.

Hepatocyte nuclear factor (HNF)-1alpha and HNF-1beta are concerned in sucrase-isomaltase (SI) gene expression, and directly bind two sites (SIF2, SIF3) of the promoter of the SI gene. However, it is not completely clear that HNF-1alpha and HNF-1beta play a role in regulation of SI gene expression. To clarify mechanisms of SI gene expression regulated by HNF-1alpha and HNF-1beta, we established four stable cell lines based on enterocyte-like cell line Caco-2, in which wild HNF-1alpha or wild HNF-1beta, or else mutant HNF-1alphaT539fsdelC or mutant HNF-1betaR177X was overexpressed. In the HNF-1alphaT539fsdelC cells and HNF-1betaR177X cells, but not in the wild HNF-1alpha cells and wild HNF-1beta cells, SI gene expression and enzyme activity were significantly diminished compared with that in Caco-2 cells. Moreover, to clarify whether or not stable cell differentiation was influenced by overexpression of these transgenes, alkaline phosphatase (ALP) gene expression and enzyme activity were measured. There were no changes in ALP gene expression or enzyme activity in these cells. These observations suggest that mutant HNF-1alphaT539fsdelC and mutant HNF-1betaR177X inhibits SI gene at the transcriptional level, resulting in decreased SI enzyme activity in Caco-2 cells. We propose that both HNF-1alpha and HNF-1beta would contribute to constitutive expression of the SI gene in the differentiated state in Caco-2 cells.

Alkaline Phosphatase↗

PubMed1981

New anthracycline metabolites from mutant strains of Streptomyces galilaeus MA144-M1. I. Isolation and characterization of various blocked mutants.

During genetic study on obtaining high-yield variants of aclacinomycin A-producer, a variety of blocked mutants were isolated from Streptomyces galilaeus MA144-M1 and were characterized. The isolated mutants included those which accumulated only specific components of parental glycosides, those which produced new aklavinone glycosides devoid of parental rhodosamine or both rhodinose and cinerulose, those which produced non-glycosidic aglycones, and antibiotic-negative mutants, some of which were able to glycosidate exogenous aklavinone. By biotransformation with the aglycone feeding culture, the precursor activity of new aglycones was also tested. From the results and in relation to the characterization of isolated mutants, the biosynthetic pathway of aclacinomycin A and related antibiotics is discussed.

Aclarubicin↗

PubMed1975

[Eremothecium ashbyii mutants resistant to 8-azaguanine. II. Mutants with different degrees of resistance to 8-azaguanine].

Guanine, unlike adenine and hypoxanthine, can not eliminate the inhibitory effect of adenine analogues on the growth and flavinogenesis of Eremothecium ashbyii. Guanine does not restore riboflavin synthesis inhibited with 5-10(-3) M 8-azaguanine. Low adenine concentrations (10(-4)-3-10(-4) M), which do not influence the inhibitory effect of 5.-10(-3) M 8-azaguanine, restore the riboflavin synthesis in combination with guanine. On the basis of the data obtained as well as the data of biochemical analysis it is concluded that the riboflavin producer studied lacks guanosinemonophosphate reductase. The mutants resistant to various concentrations of 8-azaguanine have been obtained. In all mutants resistant to 8-azaguanine the efficiency of the incorporation of 14C-guanine and 14C-adenine into mycelium is decreased as compared with the susceptible strain. The mutant Azg-R 10 resistant to high (3-10(-3) M) concentrations of 8-azaguanine, 8-azaadenine and 2,6-diaminopurine secretes inosine-like compounds when grown in a synthetic medium. The stepwise increase of the mutant resistance to 8-azaguanine from 10(-4) M TO 3-10(-3) M did not result in further enhancement of riboflavin synthesis.

Ascomycota↗

PubMed1989

Ketoconazole-resistant mutants of Microsporum gypseum. I. Isolation of mutants, biochemical methods.

The ketoconazole-resistant mutants were isolated from four strains of the dermatophyte Microsporum gypseum. The frequency of spontaneous mutants ranged within 10(-8) to 10(-9) (per spore and nucleus). The method was established for obtaining the spontaneous mutants manifested as the faster growing sectors. By means of mutagenic effect of UV radiation, the frequency of mutants increased by one order. The method used for determination of ergosterol the biosynthesis of which could be associated with the mechanism of resistance to ketoconazole is described and evaluated.

Drug Resistance, Microbial↗

PubMed1989

Bacteriorhodopsin mutants of Halobacterium sp. GRB. I. The 5-bromo-2'-deoxyuridine selection as a method to isolate point mutants in halobacteria.

Halobacterium sp. GRB (Ebert, K., Goebel, W., and Pfeifer, F. (1984) Mol. & Gen. Genet. 194, 91-97) was used to isolate bacteriorhodopsin (BR) mutants. A procedure is described which allows the enrichment of any type of mutant unable to grow under the selection conditions applied. Its use for the isolation of phototrophically negative, retinal-positive mutants of Halobacterium sp. GRB is demonstrated. Single-cell clones of this phenotype were further characterized. The expression of bacterioopsin was tested with a monoclonal antibody directed against the C terminus of the protein. The expressed bacteriorhodopsins were characterized by their specific activity for proton pumping, their spectral properties, and photocycle kinetics. About 15 independent mutants carrying bacteriorhodopsins of three distinct phenotypic classes could be isolated, including BR with a different absorption maximum, BR of lower specific activity, and BR characterized by a slower photocycle and a lack of proton pumping activity.

Bacteriorhodopsins↗

PubMed1985

[Mutability of the LYS2 gene in diploid saccharomycete yeasts. I. The occurrence of spontaneous mutants and mutants induced by x-ray and ultraviolet radiation].

More than 3000 spontaneous and induced lys2 mutants were obtained in haploid and diploid strains of yeast Saccharomyces. The ability to utilize alpha-aminoadipate was used for lys2 mutant screening. The spontaneous and induced mutation rates were measured in haploid and diploid strains. Mitotic segregation of pho1 marker linked to LYS2 was studied in lys2 mutants obtained in diploid strains. Fertility of diploid lys2 mutants was tested. The conclusion to be drawn from the data presented is that mutations appeared in one of two homologous chromosomes and then segregated by mitotic homozygotization.

Diploidy↗

PubMed1986

[Characteristics of Candida tropicalis D-2 mutants resistant to nystatin, levorin, amphotericin B. I. Frequency of induction depending on the intracellular lipid level and phenotypic characteristics of mutants].

Induction frequency of mutants of Candida tropicalis D-2 strain depends on the number of intracellular lipids and the nature of a chemical mutagen. Para-aminobenzoic acid leads to a decrease in the lethality and mutagenicity of nitrosocompounds, which is stronger expressed in cells with enhanced quantity of lipids. Among nystatin and levorin-resistant mutants obtained independently, the mutants with supersensitivity to other antibiotics were discovered. The majority of mutants possess cross-resistance.

Amphotericin B↗

PubMed1980

Replication of transformation-defective mutants of the Prague strain of Rous sarcoma virus and isolation of a td mutant from duck-adapted PR-RSV-C.

The replication of transformation-defective mutants of the Prague strain of Rous sarcoma virus subgroup C was studied using roller cultures. Under such conditions, 10(5)--10(6) infectous units of virus per 0.2 ml were produced, as revealed in both the reverse transcriptase and 16Q complementation tests. A new td daPR-RSV-C mutant was isolated from duck-adapted PR-RSV-C. This mutant replicated in roller cultures with equal efficiency as the original td PR-RSV-C. It was verified that td daPR-RSV-C does not transform chicken fibroblasts, is not oncogenic for 3-week-old chickens and has subgroup C host-range specificity. Both td mutants replicate in duck cells and reach the same titres.

Animals↗

PubMed1984

Detection of mutant-specific responses by macrophage migration inhibition reactions induced by wild-type and mutant polyoma viruses and polyoma virus-infected cells.

Macrophage migration inhibition responses of mice immunized with mutant polyoma viruses or with cells transformed and/or infected by them have been studied. The macrophage migration inhibition reaction revealed individual differences. In several cases, mice immunized with a mutant virus responded preferentially or exclusively to extracts of cells transformed or infected with the corresponding mutant. Moreover, in the macrophage migration inhibition test, mutant viruses were usually less immunogenic than were the corresponding transformed-infected cells.

Animals↗

PubMed1984

[Escherichia coli K-12 mutants with enhanced resistance to ionizing radiation. IV. Recombination characteristics of Gamr mutants].

In the radiation-resistant Gamr444 mutant the inheritance frequency of long F' episomes ORF1 (purE+ tsx+ procC+ lac+) and F'14 (ilv+--argE+) is lower, and the frequencies of chromosome mobilization and integrative suppression of temperature-sensitive dnaA46 mutation by the sex factor F are much higher than those in the wild-type strain AB1157 and another radiation-resistant mutant Gamr445. In this respect, the mutant Gamr444 is very similar to the recRC sbcB mutant (RecF-pathway of recombination).

Chromosomes, Bacterial↗

PubMed1984

[Regulatory mutants for the synthesis of a 2d purine nucleoside phosphorylase in Escherichia coli K-12. I. Synthesis inducers and the substrate specificity of purine nucleoside phosphorylase in pndR mutants].

Restoration of the ability to catabolise the purine nucleosides in phenotypic revertants of Escherichia coli K-12 mutants defective in deoD encoded purine nucleoside phosphorylase (PNPase 1) is the result of regulatory pndR mutations for synthesis of a second purine nucleoside phosphorylase (PNPase 2). In pndR+ strains synthesis of PNPase 2 is induced by xanthosine; in pndR mutants catabolising all purine nucleosides synthesis of this enzyme is constitutive; in other pndR mutants only catabolising some of purine nucleosides, this catabolisible nucleosides, namely, deoxyinosine, deoxyadenosine as well as, in some cases, inosine and adenosine, act as inducers of PNPase 2 synthesis. In some pndR mutants with inducible PNPase 2, xanthosine is a stronger inducer, in others it is weaker, in comparison with pndR+ strains. In bacterial cells PNPase 2 catalyses the phosphorolytic cleavage of adenosine, inosine, deoxyinosine, guanosine, deoxyguanosine and xanthosine, though in crude extracts adenosine and deoxyadenosine phosphorylase activities of the enzyme are not expressed.

Enzyme Induction↗

PubMed1981

[Reactivity of the H-2ba mutant against the products of the H-2Kb gene and its mutant alleles in the graft vs. host reaction and the linkage with the H-2 complex of the nonresponsiveness of B10.M mice against the H-2kbd antigen].

Five mutants for the H-2Kb gene within the mouse major histocompatibility complex were studied in the Simonsen spleen weight assay. It was shown that H-2Kba mutant was unable to react against only H-2Kbd recipients, while developed normal reaction against H-2Kbf, H-2Kbg2, H-2Kbh mutants. These results indicate the specific character of the nonresponsiveness. Mice of the B10.M (H-2f) strain do not complement the defect of reactivity in the H-2Kba mutant. Evidence from the study of G2 hybrids indicate that the gene for nonresponsiveness in B 10.M was linked with the H-2 complex.

Alleles↗

PubMed1982

[Eremothecium ashbyii mutants resistant to 8-azaguanine. III. Nucleotide pyrophosphorylase activity of mutants with a varying degree of 8-azaguanine resistance].

Eremothecium ashbyii mutants resistant to low and high concentrations of 8-azaguanine (AZG), have been obtained. In low resistant mutants (10(-4) M AZG) isolated by one step selection, the activity of GMP- and AMP-pyrophosphorylases was decreased, as compared with the initial sensitive strain. The stepwise increase of the mutants resistance to AZG resulted in increasing of resistance to 8-azaadenine and decreasing of the activity of GMP-pyrophosphorylase, while this did not affect the level of AMP-pyrophosphorylase. Characteristics of the cross-resistance of mutant to purine analogues and the level of nucleotide-pyrophosphorylases activity were discussed in the light of their possible influence on riboflavin biosynthesis.

Adenine Phosphoribosyltransferase↗

PubMed1981

[Chinese hamster cell mutant at the hypoxanthine-guanine phosphoribosyltransferase locus. I. The collection of mutants and intragene complementation experiments].

A group of 59 Chinese hamster cell clones mutant for hypoxanthine-guanine phosphoribozyl-transferase (HGPRT) is described. The clones were collected from selective media containing three purine analogs, 8-azaguanine, 6-mercaptopurine and 6-thioguanine. Spontaneous mutants of an independent origin induced by different mutagens were studied. They differed by the degree of the HGPRT enzyme activity and their ability to grow in the presence of purine analogs and on a counter-selective HAT medium. Mutant clones showed "abnormal" combinations of resistance to both types of selective media and also lacked cross-resistance to different analogs of hypoxanthine and guanine. A possibility of intragenics complementation between various clones was studied. The scheme of experiments on complementation is proposed to make the work less time-consuming by virtue of a simultaneous testing of a clone group. Having used the method, 383 clone combinations were analyzed and 13 complementing pairs of mutants. were found.

Animals↗

PubMed1994

Transfection of a nonactive site mutant murine DHFR cDNA (the tryptophan 15 mutant) into Chinese hamster ovary and mouse marrow progenitor cells imparts MTX resistance in vitro.

Chinese hamster ovary (CHO) DHFR-cells were converted to the DHFR+ (dihydrofolate reductase) phenotype when transfected with a mammalian expression vector containing the murine mutant Trp15 DHFR cDNA. Transfection of the Trp15 DHFR cDNA into wild-type CHO cells resulted in resistance to high levels of methotrexate (MTX) in vitro indicating that this mutant DHFR cDNA can act as a dominant marker. Southern and Northern blot analyses of transfected cells indicated that the transfected mutant DHFR cDNA was integrated and expressed. Gene copy number analysis showed that the Trp15 cDNA was amplifiable in increasing concentrations of MTX. Transfection of murine bone marrow progenitor cells with the Trp15 mutant DHFR cDNA resulted in MTX resistant colony forming units-granulocyte macrophage.

Animals↗

PubMed1991

CNS pathology in the neurological mutant rats zitter, tremor and zitter-tremor double mutant (spontaneously epileptic rat, SER). Exaggeration of clinical and neuropathological phenotypes in SER.

The pathological alterations in the central nervous system (CNS) were examined in three kinds of mutant rat; the zitter (zi/zi; Zi), the tremor rat (tm/tm; Tm) and the spontaneously epileptic rat (SER) which is a double mutant carrying both zitter and tremor genes. Two major alterations demonstrated in these mutants were hypomyelination and vacuolation or spongy degeneration. Hypomyelination was observed predominantly in SER and to a lesser extent in Zi, and was accompanied by a redundant or aberrant myelin sheath formation in addition to a decreased number of myelinated fibres. This appeared to be related to the occurrence of tremor. There was no abnormality in the structure of the myelin lamellae and oligodendrocytes or any destruction of myelin sheaths by phagocytic cells. The number of radial components in CNS myelin was increased almost equally in Zi, Tm and SER. Vacuolation was prominent in SER and Tm, especially in the brainstem and thalamus. Zi also developed mild vacuolation with advancing age. Vacuolation seemed to be related to the epileptic phenomena in SER and Tm. Vacuoles consisted mainly of swollen astrocytic processes and enlargement of the extracellular space, as well as occasional enlargement of periaxonal spaces. Thus both pathological findings--the hypomyelination derived from the zitter mutation with tremor, and the vacuolation from the tremor mutation with epileptic symptoms--were mutually exaggerated in SER. It is postulated that the two different genetic loci with zi and tm mutations interact and synergistically reinforce each other both clinically and pathologically in SER.

Aging↗