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You searched for +publisher:"University of Alabama – Birmingham" +contributor:("Lisa M. Guay-Woodford"). One record found.

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1. Boddu, Ravindra. Characterizing The Transcriptional Complexity Of Pkhd1/pkhd1.

Degree: 2012, University of Alabama – Birmingham

Mutations in <italic>PKHD1</italic> gene cause autosomal recessive polycystic kidney disease. Our previous studies have shown that human <italic>PKHD1</italic> and its mouse orthologue, <italic>Pkhd1</italic>, undergo an extensive pattern of alternative splicing. <italic>Pkhd1</italic> is primarily expressed in renal and biliary tubular structures. Translation products of these alternative spliced transcripts are predicted to generate isoforms expressed in plasma membrane, primary cilium and cytoplasm. We have characterized the cyli mouse model of ARPKD and identified a frameshift mutation, c.7589delGGinsT, in <italic>Pkhd1</italic> exon 48. In this thesis we have characterized the mouse <italic>Pkhd1</italic><super>cyli/cyli</super> model (liver restricted phenotype) and evaluated the transcriptome in terms of alternative exon usage and alternative splicing events. We observed that the <italic>Pkhd1</italic> transcriptional profiles were different in 18.5dpc embryonic kidney, liver and placenta as well as in multiple adult tissues. We have evaluated 41 kidney transcripts showing different patterns of <italic>Pkhd1</italic> exons splicing for WT and MUT kidney transcripts. Majority of the splicing events involved exon 6. All the transcripts analyzed appeared to preserve the amino acid sequence of the <italic>Pkhd1</italic> longest open reading frame, most of them using the original translation start site in exon 2, same as for the WT full length <italic>Pkhd1</italic>. All the novel exon junctions have been verified by RT-PCR. RNA-Seq studies in IMCD cells employing target enrichment strategy confirmed virtually all of the novel exon junctions observed in our catalogue. Analyses of exonic splice enhancers using bioinformatics and minigene experiments revealed consensus positions for serine/arginine-rich proteins (SR) that influence alternative exon usage. Site-directed mutagenesis and minigene experiments showed the importance of intronic splice enhancers and polypyrimidine tract in <italic>Pkhd1</italic> splicing. Preparation of translationally active mRNA from membrane-bound polysomal fraction showed that <italic>Pkhd1</italic> transcripts with novel exon junctions were polysome-bound and hence likely to be involved in the process of translation. Evaluation of human missense variants from Aachen mutation database for ARPKD revealed that R760H variant alters <italic>PKHD1</italic> splicing by disrupting one of the SR protein motifs. Taken together, our data demonstrate <italic>PKHD1/Pkhd1</italic> transcriptional processing is modulated in part by intragenic factors and dysregulated <italic>PKHD1</italic> splicing represents an under-appreciated pathogenic mechanism in ARPKD.

PhD

1 online resource (x, 148, [10] pages) :illustrations

Cell Biology

alternative splicing, ARPKD, kidney transcripts, mouse model, splicing…

Advisors/Committee Members: Lisa M. Guay-Woodford, Agarwal,Anupam Yoder, Bradley K. Serra, Rosa A. Bebok,Zsuzsanna.

Subjects/Keywords: Alternative Splicing<; br>; Disease Models, Animal<; br>; Kidney Tubules, Collecting – metabolism.<; br>; Polycystic Kidney, Autosomal Recessive – genetics.<; br>; Receptors, Cell Surface – genetics.<; br>; Translocation, Genetic

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Boddu, R. (2012). Characterizing The Transcriptional Complexity Of Pkhd1/pkhd1. (Thesis). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,1504

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Boddu, Ravindra. “Characterizing The Transcriptional Complexity Of Pkhd1/pkhd1.” 2012. Thesis, University of Alabama – Birmingham. Accessed October 28, 2020. http://contentdm.mhsl.uab.edu/u?/etd,1504.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Boddu, Ravindra. “Characterizing The Transcriptional Complexity Of Pkhd1/pkhd1.” 2012. Web. 28 Oct 2020.

Vancouver:

Boddu R. Characterizing The Transcriptional Complexity Of Pkhd1/pkhd1. [Internet] [Thesis]. University of Alabama – Birmingham; 2012. [cited 2020 Oct 28]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1504.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Boddu R. Characterizing The Transcriptional Complexity Of Pkhd1/pkhd1. [Thesis]. University of Alabama – Birmingham; 2012. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1504

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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