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F Propst

Publications and source records attributed to F Propst.

34 records · Page 2Linked to original sources
PubMed1990

Neuropathological changes in transgenic mice carrying copies of a transcriptionally activated Mos protooncogene.

Independent transgenic mouse lines carrying the mouse Mos protooncogene linked to a retroviral transcriptional control sequence display behavioral abnormalities including circling, head tilting, and head bobbing. This dominant phenotype shows various degrees of penetrance in different transgenic founder animals and lines. Neuronal and axonal degeneration, gliosis, and inflammatory infiltrates are found in all transgenic mouse lines in which behavioral traits are present. Recordings of auditory-evoked potentials in mice of one of these lines demonstrate that transgenic mice are deaf; in these mice spiral ganglia degenerate and most of the cochlear hair cells are absent. By using an S1 nuclease protection assay, we have detected RNA expression of the transgene in all tissues examined and, in particular, at high levels in brain. In situ hybridization experiments show that Mos expression can be detected in specific areas of the central nervous system. Lesions are present in areas with demonstrable overexpression of Mos.

Animals↗
PubMed1989

The Mos proto-oncogene maps near the centromere on mouse chromosome 4.

The Mos proto-oncogene, the cellular homolog of the transforming gene of Moloney murine sarcoma virus, was originally assigned to mouse chromosome 4 using independent panels of mouse/hamster somatic cell hybrids. By in situ hybridization to metaphase chromosomes and standard genetic backcrosses, we have confirmed this assignment and determined that Mos maps near the centromere in a region devoid of other markers. We have also identified a restriction fragment length polymorphism (RFLP) that defines two alleles of the Mos locus in selected inbred strains of laboratory mice. Using the RFLP, we determined the strain distribution pattern for the Mos gene in three sets of recombinant inbred strains and in five strains congenic for histocompatibility antigen genes localized on chromosome 4. These results establish Mos as a useful marker in a poorly characterized region of the mouse genome. In addition, these results will facilitate the genetic analysis of the Mos locus.

Alleles↗
PubMed1988

Chicken homolog of the mos proto-oncogene.

We compared the sequence and properties of the chicken mos homolog with the previously characterized mouse and human c-mos genes. Sequence analysis revealed one major open reading frame of 1,047 base pairs encoding a protein of 349 amino acids. Both the nucleotide sequence and the deduced amino acid sequence showed 62% overall homology to mouse and human c-mos, but regions of higher conservation (approximately 70%) occurred in the putative ATP-binding and kinase domains. We detected mos transcripts by Northern (RNA) analyses in RNA prepared from chicken and quail ovaries and testes. Evidence for low levels of mos RNA expression in adult chicken heart, kidney, and spleen and in the entire embryo was obtained by S1 nuclease protection experiments. In contrast to the low transforming efficiency of human c-mos when linked to a mouse retroviral long terminal repeat element, chicken c-mos transformed NIH 3T3 cells as efficiently as mouse c-mos did. We also show that chicken primary embryo fibroblasts were morphologically altered when infected with an avian retroviral vector containing the chicken c-mos coding region.

Amino Acid Sequence↗
PubMed1988

Genetic analysis and developmental regulation of testis-specific RNA expression of Mos, Abl, actin and Hox-1.4.

The pattern of Mos proto-oncogene RNA expression in the gonads of the sterile mouse mutants, dominant spotting (W), sex reversal (Sxr), testicular feminization (Tfm), hypogonadal (hpg), quaking (qk), two t-haplotypes, three X-autosomal translocations, and the YPOS strain, is consistent with its presence in haploid spermatids in the testes and in oocytes in the ovaries. In the male-sterile mouse mutants the pattern of expression of the testis-specific transcripts for Abl, actin, and the mouse homeobox Hox-1.4 genes is identical to that observed for Mos. However, during the postnatal onset of normal spermatogenesis we detected differences in the time of the appearance of the four transcripts. We detected Hox-1.4 transcripts at day 20, Mos at day 25, and Abl and actin at day 30, demonstrating a specific regulation of expression of each of these genes during haploid spermatid maturation in the mouse. Furthermore, comparison of Mos, Abl and actin RNA expression in mouse and rat testes revealed species-specific variations in the regulation of gene expression.

Actins↗
PubMed1988

Developmental regulation of ovarian-specific Mos expression.

To gain better insight into the physiologic role of the Mos proto-oncogene in mice we have been studying the cell type and developmental specificity of its expression. It was previously shown that in adult mice, Mos is transcribed predominantly in ovaries and in haploid spermatids of the testes. Using in situ hybridization techniques we now show that in the ovary, Mos is expressed in oocytes, but not in somatic cells. In these analyses Mos transcripts are not detected in primary resting oocytes, but accumulate soon after the oocyte enters the growth phase. High levels of Mos RNA are present throughout oocyte growth and maturation. Mos RNA is also abundant in ovulated eggs prior to fertilization. Following fertilization, however, there is a dramatic loss of Mos RNA, as evidenced by the failure to detect hybridization in late one-cell embryos. The narrow developmental window for Mos transcription defined by this study suggests a role for ovarian Mos in one or more of the processes of oocyte growth, meiotic maturation, ovulation, or fertilization.

Age Factors↗
PubMed1987

Defects in lens fiber differentiation are linked to c-mos overexpression in transgenic mice.

We describe three strains of transgenic mice derived by embryo microinjection of DNA consisting of a long terminal repeat (LTR) of Moloney murine sarcoma virus (Mo-MSV) linked to the murine c-mos coding sequences. Southern analysis of the genomic DNA of these strains suggested that in each case the transgene had integrated at a different chromosomal location. The strains were characterized by dominant changes in secondary lens fiber differentiation. Shortly after birth, insufficient elongation of differentiating lens fibers and lack of basement membrane secretion resulted in breakdown of the posterior lens capsule. This, in turn led to posterior protrusion and swelling of lens tissue. In the course of the first 3 weeks after birth, globular lens cells began to fill the entire anterior and posterior chambers of the eye. Concomitantly, there was massive overexpression of c-mos RNA in the lens. Whereas this construct has high transforming activity when transfected into NIH-3T3 cells, no hyperplasia or neoplasia have been observed in the affected lenses. Increased expression of c-mos RNA was not confined to the lens of the eye but has been detected in any of several tissues tested.

Animals↗
PubMed1987

c-mos proto-oncogene RNA transcripts in mouse tissues: structural features, developmental regulation, and localization in specific cell types.

c-mos RNA transcripts have been previously detected in mouse gonadal tissue and in late-term embryos. Here, we show that they are also present at low levels in placenta and in adult mouse brain, kidney, mammary gland, and epididymis. Marked differences are observed in the size of the mos RNA transcripts detected in different tissues. All transcripts appear to end at the same 3' position, and the tissue-specific size variations appear to be due to the use of different promoters. For example, the testicular and ovarian RNA transcripts initiate approximately 280 and approximately 70 base pairs, respectively, upstream from the first initiation codon, but both end at a common site downstream from the mos open reading frame. The expression of mos is developmentally regulated in gonadal tissue. Thus, the level of mos transcripts in testes is low for the first 3 weeks after birth, increases at least 10-fold around day 25, and reaches adult levels by day 30. In contrast, ovaries from preweaning mice contain a higher level of mos mRNA compared to ovaries from adult mice. In cell fractionation experiments we show that mos transcripts are present in haploid germ cells. We find that these transcripts are associated with monosomes and polysomes. The peculiar pattern of mos expression in mouse gonadal tissue suggests a role for the c-mos proto-oncogene in germ cell differentiation.

Age Factors↗
PubMed1984

A novel transposon-like repeat interrupted by an LTR element occurs in a cluster of B1 repeats in the mouse c-mos locus.

The mouse genomic locus containing the oncogene c-mos was analyzed for repetitive DNA sequences. We found a single B1 repeat 10 kb upstream and three B1 repeats 0.6 kb, 2.7 kb, and 5.4 kb, respectively, downstream from c-mos. The B1 repeat closest to c-mos contains an internal 7-bp duplication and a 18-bp insertion. Localized between the last two B1 repeats is a copy of a novel mouse repeat. Sequence comparison of three copies of this novel repeat family shows that they a) contain a conserved BglII site, b) are approximately 420 bp long, c) possess internal 50-bp polypurine tracts, and d) have structural characteristics of transposable elements. They are present in about 1500 copies per haploid genome in the mouse, but are not detectable in DNA of other mammals. The BglII repeat downstream from c-mos is interrupted by a single 632-bp LTR element. We estimate that approximately 1200 copies of this element are present per haploid genome in BALB/c mice. It shares sequence homology in the R-U5 region with an LTR element found in 129/J mice.

Animals↗
PubMed1981

Opioids, noradrenaline and GTP analogs inhibit cholera toxin activated adenylate cyclase in neuroblastoma x glioma hybrid cells.

D-Ala2-Met5-enkephalin, morphine, and noradrenaline inhibit the adenylate cyclase in homogenates of neuroblastoma x glioma hybrid cells in a dose-dependent manner even after the enzyme has been preactivated by cholera toxin. Half-maximal inhibition and extent of inhibition are the same with native or cholera toxin-activated enzyme. The inhibition caused by opioids or noradrenaline are antagonized by naloxone or phentolamine, respectively. The effect of D-Ala2-Met5-enkephalin on cholera toxin-activated enzyme is immediate in onset and rapidly reversed by the addition of naloxone. Guanyl-5'-yl-imidodiphosphate stimulates basal activity but inhibits the enzyme activated by cholera toxin or prostaglandin E1. Stimulation occurs at a concentration of 100 microM or above, inhibition even at 0.1 microM. The inhibitory effect of the non-hydrolysable GTP analog is antagonized by GTP. Guanyl-5'-yl-methylenediphosphonate, another nonhydrolysable GTP analog, inhibits basal as well as cholera toxin-stimulated or prostaglandin E1-stimulated adenylate cyclase. Other guanine derivatives such as GDP, GMP, cyclic GMP, guanyl-5'-yl-phosphoric acid amide and guanosine have no effect under the same conditions. The results may be taken as a piece of evidence for two separate guanyl nucleotide-binding sites accompanying the adenylate cyclase in the hybrid cells and mediating, respectively, stimulation and inhibition of the enzyme by hormones.

Adenylyl Cyclases↗
PubMedDate not supplied

Neurodegenerative changes including altered tau phosphorylation and neurofilament immunoreactivity in mice transgenic for the serine/threonine kinase Mos.

Transgenic mice expressing the oncogenic protein-serine/threonine kinase Mos at high levels in the brain display progressive neuronal degeneration and gliosis. Gliosis developed in parallel with the onset of postnatal transgene expression and led to a dramatic increase in the number of astrocytes positive for GFAP, vimentin, and possibly tau. Interestingly, vimentin is normally expressed only in immature or neoplastic astrocytes, but appears to be induced to high levels in Mos-transgenic, mature astrocytes. Mos can activate mitogen activated protein kinase (MAPK) and MAPK has been implicated in Alzheimer-type tau phosphorylation. In the Mos-transgenic brain we found increased levels of phosphorylation at one epitope on tau containing serines 199 and 202 (numbering according to human tau), a pattern similar but not identical to that found in Alzheimer's disease. In addition, Mos-transgenic mice express a novel neurofilament-related protein that might be a proteolytic neurofilament heavy chain degradation product. These results suggest that activation of protein phosphorylation in neurons can result in changes in cytoskeletal proteins that might contribute to neuronal degeneration.

Animals↗
PubMedDate not supplied

Expression of c-mos proto-oncogene transcripts in mouse tissues.

Valuable information about proto-oncogenes and their physiological function has been obtained by studying their expression in normal cells. However, expression of the c-mos gene, the cellular homologue of the transforming gene of Moloney murine sarcoma virus, has not been detected in normal mouse cells or tissues. The conservation of the c-mos open reading frame strongly indicates that the gene must function during some portion of the animal life cycle, and other lines of evidence suggested to us that the c-mos proto-oncogene may be expressed at very low levels in normal tissues. We have used a sensitive S1 nuclease assay to screen RNA preparations from mouse tissues and describe here the detection of c-mos-related transcripts especially in mouse embryos, testes and ovaries. The transcripts found in testis RNA are estimated to be approximately 1.7 kilobases (kb) long by Northern analysis. S1 analysis demonstrated that the entire mos open reading frame is present. In contrast, we detect approximately 1.4-kb transcripts in ovary RNA and at least two major transcripts, approximately 2.3 and approximately 1.3 kb, in embryo RNA. The latter transcripts have in common sequences of at least 1 kb, representing most of the c-mos open reading frame. The variation in size of the mos transcript in different tissues suggests a novel regulatory mechanism for the expression of this proto-oncogene.

Animals↗