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 Interaction of the murine dilute suppressor gene (dsu) with fourteen coat color mutations.

Genetics ◽  
1990 ◽  
Vol 125 (2) ◽  
pp. 421-430 ◽  
Author(s):  
K J Moore ◽  
D A Swing ◽  
N G Copeland ◽  
N A Jenkins
Keyword(s):  
Neural Crest ◽  
Coat Color ◽  
Suppressor Gene ◽  
Hair Shaft ◽  
Exact Nature ◽  
Retinal Pigmented Epithelium ◽  
Eye Color ◽  
Pigmented Epithelium ◽  
Color Phenotype ◽  
Coat Color Phenotype

Abstract The murine dilute suppressor gene, dsu, was previously shown to suppress the dilute coat color phenotypes of mice homozygous for the dilute (d), leaden (ln), and ashen (ash) mutations. Each of these mutations produce adendritic melanocytes, which results in an abnormal transportation of pigment granules into the hair shaft and a diluted coat color. The suppression of each mutation is associated with the restoration of near normal melanocyte morphology, indicating that dsu can compensate for the absence of normal d, ln and ash gene products. In experiments described here, we have determined whether dsu can suppress the coat color phenotype of 14 additional mutations, at 11 loci, that affect coat color by mechanisms other than alterations in melanocyte morphology. In no case was dsu able to suppress the coat color phenotype of these 14 mutations. This suggests that dsu acts specifically on coat color mutations that result from an abnormal melanocyte morphology. Unexpectedly, dsu suppressed the ruby eye color of ruby-eye (ru) and ruby-eye-2 (ru-2) mice, to black. The exact nature of the defect producing these two mutant phenotypes is unknown. Histological examination of the pigmented tissues of the eyes of these mice indicated that dsu suppresses the eye color by increasing the overall level of pigmentation in the choroid but not the retinal pigmented epithelium. Choroid melanocytes, like those in the skin, are derived from the neural crest while melanocytes in the retinal pigmented epithelium are derived from the optic cup. This suggests that dsu may act specifically on neural crest-derived melanocytes. These studies have thus identified a second group of genes whose phenotypes are suppressed by dsu and have provided new insights into the mechanism of action of dsu.

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.

Neurofibromin can inhibit Ras-dependent growth by a mechanism independent of its GTPase-accelerating function

1994 ◽  
Vol 14 (1) ◽  
pp. 641-645
Author(s):  
M R Johnson ◽  
J E DeClue ◽  
S Felzmann ◽  
W C Vass ◽  
G Xu ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Protein Product ◽  
Growth Inhibitory ◽  
Nf1 Gene ◽  
A Cell ◽  
Dependent Growth ◽  
Nih 3T3

The NF1 gene, which is altered in patients with type 1 neurofibromatosis, has been postulated to function as a tumor suppressor gene. The NF1 protein product neurofibromin stimulates the intrinsic GTPase activity of active GTP-bound Ras, thereby inactivating it. Consistent with a tumor suppressor function, we have found that the introduction of NF1 in melanoma cell lines that are deficient in neurofibromin inhibited their growth and induced their differentiation. In addition, overexpression of neurofibromin in NIH 3T3 cells was growth inhibitory but did not alter the level of GTP.Ras in the cells. Transformation by v-ras, whose protein product is resistant to GTPase stimulation by neurofibromin, was inhibited in a cell line overexpressing neurofibromin, while transformation by v-raf was not altered. The results demonstrate that NF1 is a tumor suppressor gene that can inhibit Ras-dependent growth by a regulatory mechanism that is independent of neurofibromin's ability to stimulate Ras GTPase.

scholarly journals MALE-SPECIFIC LETHAL MUTATIONS OF DROSOPHILA MELANOGASTER. II. PARAMETERS OF GENE ACTION DURING MALE DEVELOPMENT

Genetics ◽  
1983 ◽  
Vol 105 (4) ◽  
pp. 881-896
Author(s):  
John M Belote
Keyword(s):  
Growth Patterns ◽  
Gene Products ◽  
Wild Type ◽  
Linked Gene ◽  
Lethal Mutations ◽  
Male Specific Lethal ◽  
A Cell ◽  
Type Gene ◽  
Diploid Cells ◽  
Male Specific

ABSTRACT The male-specific lethal mutations (msl's) identify loci whose wild-type gene products are essential for male, but not female, viability. Earlier studies in which X-linked gene activities were monitored in msl/msl male larvae demonstrated that these genes are responsible for setting and/or maintaining the level of X chromosome transcription in males (i.e., they are necessary for proper dosage compensation). The present study examines several important questions concerning their mode of action during development—The results of an examination of the effects of an msl-1 deficiency on male-lethal phase and female viability suggest that this mutation is an amorph, or a severe hypomorph. The effects of rendering a fly mutant for more than one male-lethal mutation were also examined. Multiply mutant flies were no more severely affected than singly mutant ones. A gynandromorph analysis revealed that the male-limited lethality associated with msl-2 has no single lethal focus. Somatic clones of homozygous msl-2 cells were initiated at various times during development by X-ray-induced mitotic recombination. An examination of the viability, growth patterns and morphology of marked clones demonstrated that: (1) msl-2  + acts in a cell autonomous manner, (2) msl-2  + function is required not only in larval (polytene) cells as was shown in previous work but is also needed in the diploid cells that give rise to adult structures, (3) the msl-2  + gene is needed fairly late in development and perhaps continuously, (4) the msl-2 mutation does not affect sexual differentiation.

scholarly journals Genetic Variants of DICE1/INTS6 in German Prostate Cancer Families with Linkage to 13q14

2015 ◽  
Vol 95 (4) ◽  
pp. 386-389 ◽  
Author(s):  
Malte Böhm ◽  
Christiane Maier ◽  
Rainer Küfer ◽  
Albrecht Röpke ◽  
Walther Vogel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Genetic Basis ◽  
Cancer Susceptibility ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Caucasian Men ◽  
Chromosome 13Q14 ◽  
Exon 10

Introduction: Prostate cancer is the most frequent malignancy found to occur in Caucasian men, but its genetic basis remains elusive. A prostate cancer-susceptibility locus has been identified on chromosome 13q14. The tumour suppressor gene deleted in cancer cells 1 (DICE1/INTS6) is located within this interval on 13q14.3. Materials and Methods: We performed mutation analysis of the DICE1/INTS6 gene in thirteen German prostate cancer families. Results and Conclusion: None of the patients harboured DICE1 mutations, and similar frequencies of the previously identified 13 bp deletion polymorphism in the DICE1 promoter were observed in the familial prostate cancer patients as compared with sporadic prostate cancer patients and controls. However, in one family with three affected brothers, the variations c.1215A>C (p.T405T) in exon 10 and c.2568A>G (p.S856S) in exon 17 were detected in a heterozygous pattern. In sporadic prostate cancer patients, variant c.2568A>G (p.S856S) was detected in 10/325 (3.08%) compared with 5/207 (2.42%) control samples (p > 0.05). We conclude that DICE1 appears to be involved in prostate cancer progression rather than in the initiation of prostate cancer.

scholarly journals The Saccharomycescerevisiae Isw2p-Itc1p Complex RepressesINO1 Expression and Maintains Cell Morphology

2001 ◽  
Vol 183 (17) ◽  
pp. 4985-4993 ◽  
Author(s):  
Minetaka Sugiyama ◽  
Jun-Ichi Nikawa
Keyword(s):  
Leucine Zipper ◽  
Suppressor Gene ◽  
Dominant Negative ◽  
Gene Products ◽  
Truncated Form ◽  
Basic Leucine Zipper ◽  
Multicopy Suppressor ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

ABSTRACT In the yeast Saccharomyces cerevisiae, IRE1 encodes a bifunctional protein with transmembrane kinase and endoribonuclease activities. HAC1 encodes a transcription factor which has a basic leucine zipper domain. Both gene products play a crucial role in the unfolded protein response. Mutants in which one of these genes is defective also show the inositol-auxotrophic (Ino−) phenotype, but the reason for this has not been clear. To investigate the mechanism underlying the Ino−phenotype, we screened a multicopy suppressor gene which can suppress the Ino− phenotype of the Δhac1 strain. We obtained a truncated form of the ITC1 gene that has a defect in its 3′ region. Although the truncated form ofITC1 clearly suppressed the Ino− phenotype of the Δhac1 strain, the full-lengthITC1 had a moderate effect. The gene products ofITC1 and ISW2 are known to constitute a chromatin-remodeling complex (T. Tsukiyama, J. Palmer, C. C. Landel, J. Shiloach, and C. Wu, Genes Dev. 13:686–697, 1999). Surprisingly, the deletion of either ITC1 orISW2 in the Δhac1 strain circumvented the inositol requirement and caused derepression of INO1even under repression conditions, i.e., in inositol-containing medium. These data indicate that the Isw2p-Itc1p complex usually repressesINO1 expression and that overexpression of the truncated form of ITC1 functions in a dominant negative manner inINO1 repression. It is conceivable that the repressor function of this complex is regulated by the C-terminal region of Itc1p.

Activation and Supply of Channels and Pumps by Aldosterone

Physiology ◽  
1996 ◽  
Vol 11 (3) ◽  
pp. 126-133
Author(s):  
F Verrey ◽  
J Beron
Keyword(s):  
Sodium Channels ◽  
Sodium Transport ◽  
Sodium Reabsorption ◽  
Transcription Rate ◽  
Gene Products ◽  
Glucocorticoid Hormones ◽  
Early Activation ◽  
A Cell ◽  
Later Phase

Mineralocorticoid and glucocorticoid hormones stimulate sodium reabsorption across target epithelia by modulating the transcription rate of a cell-specific set of genes. Unidentified regulated gene products mediate an early activation of preexisting sodium channels and pumps. In a later phase, the supply of proteins belonging to the sodium-transport machinery is increased.

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