20 research outputs found
Characterization of the OFD1/Ofd1 genes on the human and mouse sex chromosomes and exclusion of Ofd1 for the Xpl mouse mutant
No full textCharacterization of the OFD1/Ofd1 genes on the human and mouse sex chromosomes and exclusion of Ofd1 for the Xpl mouse mutant
No full textCharacterization of the OFD1/Ofd1 genes on the human and mouse sex chromosomes and exclusion of Ofd1 for the Xpl mouse mutant
No full textCharacterization of the OFD1/Ofd1 genes on the human and mouse sex chromosomes and exclusion of Ofd1 for the Xpl mouse mutant
No full textA novel liver specific isoform of the rat LAR transcript is expressed as a truncated isoform encoded from a 5 ' UTR located within intron 11
No full textBackground: The leukocyte common antigen related receptor (LAR) protein has been shown to modulate the signal transduction of a number of different growth factors, including insulin and insulin-like growth factor 1. Splice variants exhibit differing roles and are expressed according to tissue type and developmental stage.
Results: Using 5'RACE, we identified a 5'UTR within intron 11 of the rat LAR gene. We demonstrated that this gives rise to a novel isoform of the LAR transcript encoded from the identified region within intron 11. By priming across the site from exon 11 to exon 15 we show that the novel 5'UTR is not represented in the full-length transcript and thus, it produces a truncated form of the LAR mRNA. We examined the tissue distribution of this novel isoform and
found it to be exclusively expressed in liver. We additionally identified a liver specific 150 kDa band
with western blotting which we propose may represent the protein product of the novel transcript. Luciferase assays showed the region immediately upstream of the 5'UTR to possesses considerable promoter activity and that this may be conferred by the presence of a number of putative binding
sites for liver enriched transcription factors.
Conclusion: In summary, we describe a novel, liver specific, truncated isoform of the LAR transcript transcribed under the control of an intronic promoter, potentially representing a previously unidentified modulator of hepatic insulin signalling
The mouse Midl gene: implications for the pathogenesis of Opitz syndrome and the evolution of the mammalian pseudoautosomal region
No full textA Transgenic Mouse Model of Merkel Cell Virus Small Tumor Antigen
No full textMerkel cell carcinoma (MCC), a primary cutaneous neoplasm, originates in the mechanoreceptor Merkel cells in the basal layer of the epidermis. Risk factors include UV exposure, advanced age and immunosuppression, suggesting an infectious etiology. MCC
incidence in the US is rising, with approximately 1500 cases per year. The non-enveloped, double-stranded DNA Merkel cell polyomavirus (MCV) is responsible for approximately 80% of MCC cases. The virus was discovered by subjecting MCC tissue samples to digital transcriptome subtraction, in which mRNA is isolated, the human transcripts subtracted in silico and the remaining transcripts compared to viral sequences.
MCV expresses differentially spliced Large (LT), Small (sT) and 57 kT tumor antigens from the T antigen early locus, similar to other polyomaviruses such as SV40. Both LT and sT are critical for transformation. LT is a helicase responsible for replication of the viral genome, however in integrated viral genomes it is either truncated or mutated to eliminate its replicative functions. sT contributes to transformation via hyperphosphorylation and inhibition of the cap-dependent translation inhibitor 4E-BP1. The function of 57 kT remains unknown. Knockdown of LT induces necroptosis of MCVpositive MCC cells, whereas sT expression in rodent Rat-1 cells is transformative.
Being that sT is the transformative agent in rodent cells, it would be of interest to develop a mouse model expressing sT in a tissue-specific manner to determine whether tumor formation occurs. Indeed, several mouse models of SV40 T antigen have been developed over the past decades, each resulting in tissue-specific tumor formation. We developed a MCV sT transgenic mouse model, in which a lox-stop-lox sT is expressed via an ER-inducible Cre gene under the control of the ubiquitin promoter. Upon tamoxifen induced MCV sT expression, ER-Cre-positive mice demonstrate severe weight loss, ruffled fur and a hunched posture, necessitating euthanasia. Western blotting reveals sT expression in several tissues, whereas TUNEL staining shows significant cell death. While
we were unable to observe transformation, we believe this drastic phenotype demonstrates the validity of our MCV sT transgenic mouse model and warrants further investigation into the mechanism of death
Is the Y chromosome disappearing?—Both sides of the argument
No full textOn August 31, 2011 at the 18th International Chromosome Conference in Manchester, Jenny Graves took on Jenn Hughes to debate the demise (or otherwise) of the mammalian Y chromosome. Sex chromosome evolution is an example of convergence; there are numerous examples of XY and ZW systems with varying degrees of differentiation and isolated examples of the Y disappearing in some lineages. It is agreed that the Y was once genetically identical to its partner and that the present-day human sex chromosomes retain only traces of their shared ancestry. The euchromatic portion of the male-specific region of the Y is ~1/6 of the size of the X and has only ~1/12 the number of genes. The big question however is whether this degradation will continue or whether it has reached a point of equilibrium. Jenny Graves argued that the Y chromosome is subject to higher rates of variation and inefficient selection and that Ys (and Ws) degrade inexorably. She argued that there is evidence that the Y in other mammals has undergone lineage-specific degradation and already disappeared in some rodent lineages. She also pointed out that there is practically nothing left of the original human Y and the added part of the human Y is degrading rapidly. Jenn Hughes on the other hand argued that the Y has not disappeared yet and it has been around for hundreds of millions of years. She stated that it has shown that it can outsmart genetic decay in the absence of "normal" recombination and that most of its genes on the human Y exhibit signs of purifying selection. She noted that it has added at least eight different genes, many of which have subsequently expanded in copy number, and that it has not lost any genes since the human and chimpanzee diverged ~6 million years ago. The issue was put to the vote with an exact 50/50 split among the opinion of the audience; an interesting (though perhaps not entirely unexpected) skew however was noted in the sex ratio of those for and against the notion
EFFECT OF CARBON-DIOXIDE AND HYDROSTATIC-PRESSURE ON THE PH OF CULTURE MEDIA AND THE GROWTH OF METHANOGENS AT ELEVATED-TEMPERATURE
No full textCytoplasmic islet cell antibodies recognize distinct islet antigens in IDDM but not in stiff man syndrome
No full textCytoplasmic islet cell antibodies are well-established predictive markers of IDDM. Although target molecules of ICA have been suggested to be gangliosides, human monoclonal ICA of the immunoglobulin G class (MICA 1-6) produced from a patient with newly diagnosed IDDM recognized glutamate decarboxylase as a target antigen. Here we analyzed the possible heterogeneity of target antigens of ICA by subtracting the GAD-specific ICA staining from total ICA staining of sera. This was achieved 1) by preabsorption of ICA+ sera with recombinant GAD65 and/or GAD67 expressed in a baculovirus system and 2) by ICA analysis of sera on mouse pancreas, as GAD antibodies do not stain mouse islets in the immunofluorescence test. We show that 24 of 25 sera from newly diagnosed patients with IDDM recognize islet antigens besides GAD. In contrast, GAD was the only islet antigen recognized by ICA from 7 sera from patients with stiff man syndrome. Two of these sera, however, recognized antigens besides GAD in Purkinje cells. In patients with IDDM, non-GAD ICA were diverse. One group, found in 64% of the sera, stained human and mouse islets, whereas the other group of non-GAD ICA was human specific. Therefore, mouse islets distinguish two groups of non-GAD ICA and lack additional target epitopes of ICA besides GAD. Longitudinal analysis of 6 sera from nondiabetic ICA+ individuals revealed that mouse-reactive ICA may appear closer to clinical onset of IDDM in some individuals
