Base Substitution at Different Alternative Splice Donor Sites of the Tyrosinase Gene in Murine Albinism

Fur, Nathalie Le; Kelsall, Stephen R.; Mintz, Beatrice

doi:10.1006/geno.1996.0551

Cited by 50 publications

(38 citation statements)

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“…1). The tyrosinase protein was virtually absent in c 2j ͞c 2j skin, possibly due to proteolytic degradation (20). In c 2j ͞c 2j primary melanomas and their metastases, absolute levels of the full-length transcript varied but were higher in most cases than in c 2j ͞c 2j skin (Figs.…”

Section: Resultsmentioning

confidence: 96%

“…At the same time, the usage of the next downstream alternative splice donor site within exon 1 is enhanced approximately 7-fold in c 2j over that in wild-type skin, resulting in increased levels of ⌬1c and ⌬1d mRNAs in c 2j ͞c 2j skin. However, the absolute levels of ⌬1c transcripts are low in any case (20). The results for skin melanocytes that are relevant for the melanoma analyses are included in Fig.…”

Section: Resultsmentioning

confidence: 98%

“…This was not as high as the 2.4-fold average increase of ⌬1d in C͞C primary melanomas over the level in C͞C skin. One might have expected a greater increase in c 2j ͞c 2j melanomas in view of the fact that the ⌬1d level was 7-fold higher in c 2j ͞c 2j skin than in C͞C skin-the result of increased activation of a splice donor site in exon 1 located downstream of the site inactivated by the c 2j mutation (20).…”

Section: Discussionmentioning

confidence: 99%

“…The c 2j albino mutation at the mouse tyrosinase locus provides an interesting opportunity of this sort, because the mutation changes the pattern of pre-mRNA splicing in comparison with that of the wild-type tyrosinase gene (20). The c 2j mutation arose spontaneously in the C57BL͞6 strain.…”

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confidence: 99%

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Up-regulation of specific tyrosinase mRNAs in mouse melanomas with the c ^2j gene substituted for the wild-type tyrosinase allele: Utilization in design of syngeneic immunotherapy models

Fur¹,

Silvers²,

Kelsall³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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The expression of cell-specialization genes is likely to be changing in tumor cells as their differentiation declines. Functional changes in these genes might yield unusual peptide epitopes with anti-tumor potential and could occur without modification in the DNA sequence of the gene. Melanomas undergo a characteristic decline in melanization that may ref lect altered contributions of key melanocytic genes such as tyrosinase. Quantitative reverse transcriptase-PCR of the wild-type (C) tyrosinase gene in transgenic (C57BL͞6 strain) mouse melanomas has revealed a shift toward alternative splicing of the pre-mRNA that generated increased levels of the ⌬1b and ⌬1d mRNA splice variants. The spontaneous c 2j albino mutation of tyrosinase (in the C57BL͞6 strain) changes the pre-mRNA splicing pattern. In c 2j ͞c 2j melanomas, alternative splicing was again increased. However, while some mRNAs (notably ⌬1b) present in C͞C were obligatorily absent, others (⌬3 and ⌬1d) were elevated. In c 2j ͞c 2j melanomas, the percentage of total tyrosinase transcripts attributable to ⌬3 reached approximately 2-fold the incidence in c 2j ͞c 2j or C͞C skin melanocytes. The percentage attributable to ⌬1d rose to approximately 2-fold the incidence in c 2j ͞c 2j skin, and to 10-fold that in C͞C skin. These differences provide a basis for unique mouse models in which the melanoma arises in skin grafted from a C͞C or c 2j ͞c 2j transgenic donor to a transgenic host of the same or opposite tyrosinase genotype. Immunotherapy designs then could be based on augmenting those antigenic peptides that are novel or overrepresented in a tumor relative to the syngeneic host.

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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Up-regulation of specific tyrosinase mRNAs in mouse melanomas with the c ^2j gene substituted for the wild-type tyrosinase allele: Utilization in design of syngeneic immunotherapy models

Fur¹,

Silvers²,

Kelsall³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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“…In this study we targeted the region around the tyrosinase locus ( Tyr) because the arrangements in this region should be non‐lethal and Tyr provides the ability to score re‐arrangements phenotypically (Deol et al ., 1986; Le Fur et al ., 1996; Mintz, 1967). The zygotes used in this study were C57BL6/N, thus homozygous loss‐of‐function mutations will be readily visible as albino fur (Supporting Information Fig.…”

Section: Resultsmentioning

confidence: 99%

Chromosome engineering in zygotes with CRISPR/Cas9

Boroviak

Doe

Banerjee

et al. 2016

Genesis

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SUMMARYDeletions, duplications, and inversions of large genomic regions covering several genes are an important class of disease causing variants in humans. Modeling these structural variants in mice requires multistep processes in ES cells, which has limited their availability. Mutant mice containing small insertions, deletions, and single nucleotide polymorphisms can be reliably generated using CRISPR/Cas9 directly in mouse zygotes. Large structural variants can be generated using CRISPR/Cas9 in ES cells, but it has not been possible to generate these directly in zygotes. We now demonstrate the direct generation of deletions, duplications and inversions of up to one million base pairs by zygote injection. genesis 54:78–85, 2016. © 2016 The Authors. genesis Published by Wiley Periodicals, Inc.

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Strain differences in illumination‐dependent structural changes at mouse photoreceptor ribbon synapses

Fuchs

Sendelbeck

Atorf

et al. 2012

J of Comparative Neurology

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Photoreceptor cells encode light signals over a wide range of intensities with graded changes in their membrane potential. At their highly specialized ribbon synapses they transmit the signals to the postsynaptic neurons by the tonic release of glutamate, which is continuously adjusted to changes in light intensity. Such a level of performance requires adaptive mechanisms, and it is suggested that illumination-dependent changes in ribbon shape and size are one of these adaptive processes. In this study we compared structural properties of synaptic ribbons under various illumination conditions between three mouse strains: the pigmented C57BL/6 and the two albino strains Balb/c and B6(Cg)-Tyr(c-2J) /J (coisogenic to C57BL/6). In addition, electroretinograms (ERGs) recorded in the same groups were compared. In the C57BL/6 mouse a change in illumination did not result in structural alterations of the synaptic ribbon. Similarly, in the B6(Cg)-Tyr(c-2J) /J mouse only minor structural changes were detected. In contrast, the state of adaptation had a large influence on the ribbon structure of the Balb/c mouse. The ERG recordings showed only small functional differences between C57BL/6 and B6(Cg)-Tyr(c-2J) /J mice, but the retinal function of Balb/c mice was strongly compromised. We conclude that illumination-dependent changes of photoreceptor ribbon structure differ between strains and thus cannot be regarded as a general mechanism for light adaptation.

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Base Substitution at Different Alternative Splice Donor Sites of the Tyrosinase Gene in Murine Albinism

Cited by 50 publications

References 5 publications

Up-regulation of specific tyrosinase mRNAs in mouse melanomas with the c ^2j gene substituted for the wild-type tyrosinase allele: Utilization in design of syngeneic immunotherapy models

Up-regulation of specific tyrosinase mRNAs in mouse melanomas with the c ^2j gene substituted for the wild-type tyrosinase allele: Utilization in design of syngeneic immunotherapy models

Chromosome engineering in zygotes with CRISPR/Cas9

Strain differences in illumination‐dependent structural changes at mouse photoreceptor ribbon synapses

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Base Substitution at Different Alternative Splice Donor Sites of the Tyrosinase Gene in Murine Albinism

Cited by 50 publications

References 5 publications

Up-regulation of specific tyrosinase mRNAs in mouse melanomas with the c 2j gene substituted for the wild-type tyrosinase allele: Utilization in design of syngeneic immunotherapy models

Up-regulation of specific tyrosinase mRNAs in mouse melanomas with the c 2j gene substituted for the wild-type tyrosinase allele: Utilization in design of syngeneic immunotherapy models

Chromosome engineering in zygotes with CRISPR/Cas9

Strain differences in illumination‐dependent structural changes at mouse photoreceptor ribbon synapses

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Up-regulation of specific tyrosinase mRNAs in mouse melanomas with the c ^2j gene substituted for the wild-type tyrosinase allele: Utilization in design of syngeneic immunotherapy models

Up-regulation of specific tyrosinase mRNAs in mouse melanomas with the c ^2j gene substituted for the wild-type tyrosinase allele: Utilization in design of syngeneic immunotherapy models