scholarly journals The murine dilute suppressor gene dsu suppresses the coat-color phenotype of three pigment mutations that alter melanocyte morphology, d, ash and ln.

Genetics ◽  
1988 ◽  
Vol 119 (4) ◽  
pp. 933-941
Author(s):  
K J Moore ◽  
D A Swing ◽  
E M Rinchik ◽  
M L Mucenski ◽  
A M Buchberg ◽  
...  
Keyword(s):  
Coat Color ◽  
Suppressor Gene ◽  
Chromosome 9 ◽  
Chromosome 1 ◽  
Wild Type ◽  
Mapping Data ◽  
Partial Restoration ◽  
Normal Melanocyte ◽  
Partial Suppression ◽  
Pigment Genes

Abstract The murine dilute suppressor gene, dsu, was identified because of its ability to suppress the dilute coat color of mice homozygous for the retrovirally induced allele (dv) of the dilute locus (d). dsu is unlinked to the d locus and has recently been shown to be semidominantly inherited. The dilute phenotype of d/d mice is the consequence of abnormal melanocyte morphology. While wild-type melanocytes are dendritic, d/d melanocytes are adendritic. dsu apparently suppresses the dilute phenotype by restoring normal melanocyte morphology. In addition to d, two other loci, ashen (ash) and leaden (ln), have been identified that produce a diluted coat color associated with adendritic melanocytes. Interestingly, d and ash are closely linked on chromosome 9 while dsu and ln are located on chromosome 1. In experiments described here, we present genetic mapping data between ash and d indicating that, despite their identical phenotypes, they are separate genes and are not intragenic complementing alleles of the same locus. We also show that dsu is only loosely linked to ln (approximately 9 cM proximal) and that dsu can suppress, at least partially, the coat color of ln/ln mice and ash/ash mice. The partial suppression of ln and ash coat colors is associated with the partial restoration of normal melanocyte morphology. These studies provide new insights into the mechanism of action of dsu and into the interrelationships between members of a family of pigment genes.

The murine dilute suppressor gene encodes a cell autonomous suppressor.

Genetics ◽  
1994 ◽  
Vol 138 (2) ◽  
pp. 491-497
Author(s):  
K J Moore ◽  
D A Swing ◽  
N G Copeland ◽  
N A Jenkins
Keyword(s):  
Positional Cloning ◽  
Genetic Basis ◽  
Coat Color ◽  
Suppressor Gene ◽  
Gene Products ◽  
Normal Melanocyte ◽  
Cell Processes ◽  
A Cell ◽  
Map Location ◽  
Coat Color Phenotype

Abstract The murine dilute suppressor gene (dsu) suppresses the coat-color phenotype of three pigment mutations, dilute (d), ashen (ash) and leaden (ln), that each produce adendritic melanocytes. Suppression is due to the ability of dsu to partially restore (ash and ln), or almost completely restore (d), normal melanocyte morphology. While the ash and ln gene products have yet to be identified, the d gene encodes a novel myosin heavy chain (myosin 12), which is speculated to be necessary for the elaboration, maintenance, and/or function of melanocyte cell processes. To begin to discriminate between different models of dsu action, we have produced aggregation chimeras between mice homozygous for dsu and mice homozygous for d to determine if dsu acts cell autonomously or cell nonautonomously. In addition, we have further refined the map location of dsu in order to examine a number of possible dsu candidate genes mapping in the region and to provide a genetic basis for the positional cloning of dsu.

scholarly journals Antitumor Effects of PRIMA-1 and PRIMA-1Met (APR246) in Hematological Malignancies: Still a Mutant P53-Dependent Affair?

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 98
Author(s):  
Paola Menichini ◽  
Paola Monti ◽  
Andrea Speciale ◽  
Giovanna Cutrona ◽  
Serena Matis ◽  
...  
Keyword(s):  
Hematological Malignancies ◽  
Cell Metabolism ◽  
Therapy Response ◽  
Tp53 Gene ◽  
Suppressor Gene ◽  
Lower Percentage ◽  
Mutant P53 ◽  
Wild Type ◽  
Antitumor Effects ◽  
Tp53 Tumor Suppressor Gene

Because of its role in the regulation of the cell cycle, DNA damage response, apoptosis, DNA repair, cell migration, autophagy, and cell metabolism, the TP53 tumor suppressor gene is a key player for cellular homeostasis. TP53 gene is mutated in more than 50% of human cancers, although its overall dysfunction may be even more frequent. TP53 mutations are detected in a lower percentage of hematological malignancies compared to solid tumors, but their frequency generally increases with disease progression, generating adverse effects such as resistance to chemotherapy. Due to the crucial role of P53 in therapy response, several molecules have been developed to re-establish the wild-type P53 function to mutant P53. PRIMA-1 and its methylated form PRIMA-1Met (also named APR246) are capable of restoring the wild-type conformation to mutant P53 and inducing apoptosis in cancer cells; however, they also possess mutant P53-independent properties. This review presents the activities of PRIMA-1 and PRIMA-1Met/APR246 and describes their potential use in hematological malignancies.

Developmental defects in gorlin syndrome related to a putative tumor suppressor gene on chromosome 9

Cell ◽  
1992 ◽  
Vol 69 (1) ◽  
pp. 111-117 ◽  
Author(s):  
Mae R. Gailani ◽  
Sherri J. Bale ◽  
David J. Leffell ◽  
John J. DiGiovanna ◽  
Gary L. Peck ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Chromosome 9 ◽  
Gorlin Syndrome ◽  
Developmental Defects ◽  
Putative Tumor Suppressor Gene ◽  
Putative Tumor Suppressor

scholarly journals Dysfunction of the TP53 tumor suppressor gene in lymphoid malignancies

Blood ◽  
2012 ◽  
Vol 119 (16) ◽  
pp. 3668-3683 ◽  
Author(s):  
Zijun Y. Xu-Monette ◽  
L. Jeffrey Medeiros ◽  
Yong Li ◽  
Robert Z. Orlowski ◽  
Michael Andreeff ◽  
...  
Keyword(s):  
Tp53 Gene ◽  
Suppressor Gene ◽  
Wild Type ◽  
Lymphoid Malignancies ◽  
The Status ◽  
Tp53 Tumor Suppressor Gene ◽  
P53 Activation ◽  
Apoptotic Pathways ◽  
P53 Inactivation ◽  
Tp53 Pathway

AbstractMutations of the TP53 gene and dysregulation of the TP53 pathway are important in the pathogenesis of many human cancers, including lymphomas. Tumor suppression by p53 occurs via both transcription-dependent activities in the nucleus by which p53 regulates transcription of genes involved in cell cycle, DNA repair, apoptosis, signaling, transcription, and metabolism; and transcription-independent activities that induces apoptosis and autophagy in the cytoplasm. In lymphoid malignancies, the frequency of TP53 deletions and mutations is lower than in other types of cancer. Nonetheless, the status of TP53 is an independent prognostic factor in most lymphoma types. Dysfunction of TP53 with wild-type coding sequence can result from deregulated gene expression, stability, and activity of p53. To overcome TP53 pathway inactivation, therapeutic delivery of wild-type p53, activation of mutant p53, inhibition of MDM2-mediated degradation of p53, and activation of p53-dependent and -independent apoptotic pathways have been explored experimentally and in clinical trials. We review the mechanisms of TP53 dysfunction, recent advances implicated in lymphomagenesis, and therapeutic approaches to overcoming p53 inactivation.

Multiple Congenital Ocular Anomalies in a silver coat Missouri Fox Trotter stallion

2021 ◽  
Vol 49 (05) ◽  
pp. 350-354
Author(s):  
Verena Maria Herb ◽  
Verena Zehetner ◽  
Klaas-Ole Blohm
Keyword(s):  
Missense Mutation ◽  
Coat Color ◽  
Incidental Finding ◽  
Unknown Origin ◽  
Allelic Frequency ◽  
Cystic Lesions ◽  
Wild Type Allele ◽  
Wild Type ◽  
Type Allele ◽  
Phenotype Characterization

AbstractThis is the first description of Multiple Congenital Ocular Anomalies (MCOA) in a silver coat Missouri Fox Trotter determined to be heterozygous for the Silver PMEL17 missense mutation associated with MCOA and a silver coat in other breeds. The stallion was treated for meningoencephalitis and bilateral uveitis of unknown origin. A complete ophthalmic examination and ocular ultrasonography were performed. As an incidental finding, the patient exhibited bilateral cystic lesions restricted to the temporal anterior uvea consistent with the Cyst phenotype and was genotyped heterozygous for the Silver mutation. Additionally, 4 other non-silver colored Missouri Fox Trotters were genotyped homozygous for the wild-type allele. Screening for PMEL17 mutation in Missouri Fox Trotters accompanied by ophthalmic phenotype characterization is recommended to determine the allelic frequency and facilitate informed breeding decisions since the silver coat color is particularly popular.

Elevated transforming growth factor β2 enhances apoptosis and contributes to abnormal outflow tract and aortic sac development in retinoic X receptor α knockout embryos

Development ◽  
2002 ◽  
Vol 129 (3) ◽  
pp. 733-746
Author(s):  
Steven W. Kubalak ◽  
D. Reneé Hutson ◽  
Karen K. Scott ◽  
Rebecca A. Shannon
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Qualitative Difference ◽  
Outflow Tract ◽  
Brdu Incorporation ◽  
Wild Type ◽  
Endocardial Cushions ◽  
Precise Integration ◽  
Partial Restoration ◽  
Transforming Growth Factor Β2

Septation of the single tubular embryonic outflow tract into two outlet segments in the heart requires the precise integration of proliferation, differentiation and apoptosis during remodeling. Lack of proper coordination between these processes would result in a variety of congenital cardiac defects such as those seen in the retinoid X receptor α knockout (Rxra–/–) mouse. Rxra–/– embryos exhibit lethality between embryonic day (E) 13.5 and 15.5 and harbor a variety of conotruncal and aortic sac defects making it an excellent system to investigate the molecular and morphogenic causes of these cardiac malformations. At E12.5, before the embryonic lethality, we found no qualitative difference between wild type and Rxra–/– proliferation (BrdU incorporation) in outflow tract cushion tissue but a significant increase in apoptosis as assessed by both TUNEL labeling in paraffin sections and caspase activity in trypsin-dispersed hearts. Additionally, E12.5 embryos demonstrated elevated levels of transforming growth factor β2 (TGFβ2) protein in multiple cell lineages in the heart. Using a whole-mouse-embryo culture system, wild-type E11.5 embryos treated with TGFβ2 protein for 24 hours displayed enhanced apoptosis in both the sinistroventralconal cushion and dextrodorsalconal cushion in a manner analogous to that observed in the Rxra–/–. TGFβ2 protein treatment also led to malformations in both the outflow tract and aortic sac. Importantly, Rxra–/– embryos that were heterozygous for a null mutation in the Tgfb2 allele exhibited a partial restoration of the elevated apoptosis and of the malformations. This was evident at both E12.5 and E13.5. The data suggests that elevated levels of TGFβ2 can (1) contribute to abnormal outflow tract morphogenesis by enhancing apoptosis in the endocardial cushions and (2) promote aortic sac malformations by interfering with the normal development of the aorticopulmonary septum.

scholarly journals Cloning and Mapping of a Putative Barley NADPH-Dependent HC-Toxin Reductase

1997 ◽  
Vol 10 (2) ◽  
pp. 234-239 ◽  
Author(s):  
F. Han ◽  
A. Kleinhofs ◽  
A. Kilian ◽  
S. E. Ullrich
Keyword(s):  
Plant Species ◽  
Chromosome 9 ◽  
Immature Embryos ◽  
Chromosome 1 ◽  
Grass Species ◽  
Cochliobolus Carbonum ◽  
Wide Range ◽  
Young Leaves ◽  
High Conservation ◽  
Hc Toxin

The NADPH-dependent HC-toxin reductase (HCTR), encoded by Hm1 in maize, inactivates HC-toxin produced by the fungus Cochliobolus carbonum, and thus confers resistance to the pathogen. The fact that C. carbonum only infects maize (Zea mays) and is the only species known to produce HC-toxin raises the question: What are the biological functions of HCTR in other plant species? An HCTR-like enzyme may function to detoxify toxins produced by pathogens which infect other plant species (R. B. Meeley, G. S. Johal, S. E. Briggs, and J. D. Walton, Plant Cell, 4:71–77, 1992). Hm1 homolog in rice (Y. Hihara, M. Umeda, C. Hara, Q. Liu, S. Aotsuka, K. Toriyama, and H. Uchimiya, unpublished) and HCTR activity in barley, wheat, oats and sorghum have been reported (R. B. Meeley and J. D. Walton, Plant Physiol. 97:1080–1086, 1993). To investigate the sequence conservation of Hm1 and HCTR in barley and the possible relationship of barley Hm1 homolog to the known disease resistance genes, we cloned and mapped a barley (Hordeum vulgare) Hm1-like gene. A putative full-length cDNA clone, Bhm1-18, was isolated from a cDNA library consisting of mRNA from young leaves, inflorescences, and immature embryos. This 1,297-bp clone encodes 363 amino acids which show great similarity (81.6%) with the amino acid sequence of HM1 in maize. Two loci were mapped to barley molecular marker linkage maps with Bhm1-18 as the probe; locus A (Bhm1A) on the long arm of chromosome 1, and locus B (Bhm1B) on the short arm of chromosome 1 which is syntenic to maize chromosome 9 containing the Hm2 locus. The Bhm1-18 probe hybridized strongly to a Southern blot of a wide range of grass species, indicating high conservation of HCTR at the DNA sequence level among grasses. The HCTR mRNA was detected in barley roots, leaves, inflorescences, and immature embryos. The conservation of the HCTR sequence, together with its expression in other plant species (R. B. Meeley and J. D. Walton, Plant Physiol. 97:1080–1086, 1993), suggests HCTR plays an important functional role in other plant species.

scholarly journals Wilms' Tumor Gene (WT1) Competes With Differentiation-Inducing Signal in Hematopoietic Progenitor Cells

Blood ◽  
1998 ◽  
Vol 91 (8) ◽  
pp. 2969-2976 ◽  
Author(s):  
Kazushi Inoue ◽  
Hiroya Tamaki ◽  
Hiroyasu Ogawa ◽  
Yoshihiro Oka ◽  
Toshihiro Soma ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Tumor Suppressor ◽  
Progenitor Cells ◽  
Wilms Tumor ◽  
Suppressor Gene ◽  
Hematopoietic Progenitor Cells ◽  
Wt1 Gene ◽  
Wild Type ◽  
Hematopoietic Progenitor ◽  
Oncogenic Function

The WT1 gene is a tumor-suppressor gene that was isolated as a gene responsible for Wilms' tumor, a childhood kidney neoplasm. We have previously reported that the WT1 gene is strongly expressed in leukemia cells with an increase in its expression levels at relapse and an inverse correlation between its expression levels and prognosis, thus making it a novel tumor marker for leukemic blast cells. Furthermore, WT1 antisense oligomers have been found to inhibit the growth of leukemic cells. These results strongly suggested the involvement of the WT1 gene in human leukemogenesis. The present study was performed to prove our hypothesis that the WT1 gene plays a key role in leukemogenesis and performs an oncogenic function in hematopoietic progenitor cells, rather than a tumor-suppressor gene function. 32D cl3, an interleukin-3–dependent myeloid progenitor cell line, differentiates into mature neutrophils in response to granulocyte colony-stimulating factor (G-CSF). However, when transfected wild-type WT1 gene was constitutively expressed in 32D cl3, the cells stopped differentiating and continued to proliferate in response to G-CSF. As for signal transduction mediated by G-CSF receptor (G-CSFR), Stat3α was constitutively activated in wild-type WT1-infected 32D cl3 in response to G-CSF, whereas, in WT1-uninfected 32D cl3, activation of Stat3α was only transient. However, most interesting was the fact that G-CSF stimulation resulted in constitutive activation of Stat3β only in wild-type WT1-infected 32D cl3, but not in WT1-uninfected 32D cl3. Thus, WT1 expression constitutively activated both Stat3α and Stat3β. A transient activation of Stat1 was detected in both wild-type WT1-infected and uninfected 32D cl3 after G-CSF stimulation, but no difference in its activation was found. No activation of MAP kinase was detected in both wild-type WT1-infected and uninfected 32D cl3 after G-CSF stimulation. These results demonstrated that WT1 expression competed with the differentiation-inducing signal mediated by G-CSFR and constitutively activated Stat3, resulting in the blocking of differentiation and subsequent proliferation. Therefore, the data presented here support our hypothesis that the WT1 gene plays an essential role in leukemogenesis and performs an oncogenic function in hematopoietic progenitor cells and represent the first demonstration of an important role of the WT1 gene in signal transduction in hematopoietic progenitor cells.

scholarly journals A new sex factor ofPseudomonas aeruginosa

1973 ◽  
Vol 21 (3) ◽  
pp. 263-272 ◽  
Author(s):  
J. M. Pemberton ◽  
B. W. Holloway
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Structural Gene ◽  
Suppressor Gene ◽  
Genetic Determinant ◽  
Sex Factors ◽  
Wild Type ◽  
Leucine Biosynthesis ◽  
Different Types ◽  
A Site ◽  
Type Strains

SUMMARYOf 150 wild-type strains ofPseudomonas aeruginosaexamined, 48 formed recombinants when mated toP. aeruginosastrain PAO FP−and hence presumably possess sex factors. Three different types of sex factor were distinguished by the pattern of transfer of particular markers in different regions of the chromosome and by the ability to confer resistance to mercury in strain PAO. One new sex factor, FP39, was studied in detail, and while similar to the previously studied FP2 in terms of transfer kinetics, natural stability and resistance to curing by acridines, it differed from FP2 in promoting chromosome transfer from a site 10 min to the left of the FP2 origin and in showing apparently aberrant entry kinetics for a leucine marker situated 48 min from the FP2 origin. This was due to FP39 having a genetic determinant either for a structural gene of leucine biosynthesis or a specific suppressor gene for this locus. PAO strains carrying both FP2 and FP39 were unstable for both sex factors, suggesting a relationship between them.

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