A Novel Role For Dyrk1A In Kidney Development

<p>Congenital anomalies of the kidney and urinary tract (CAKUT) are a leading cause of pediatric kidney failure and encompass a wide range of structural malformations resulting from defects in morphogenesis. CAKUT occur in ∼1/500 live births and with an average wait time of 3-5 years for a kidney transplant, the need is high for the development of new strategies aimed at reducing the incidence of CAKUT and preserving renal function. Approximately 14% of CAKUT cases have a known genetic component. This low causality suggests that CAKUT is complex and that there are underlying genes and mechanisms which lead to CAKUT that have not been identified. Next-generation sequencing has uncovered a significant number of putative causal genes, including the novel observation that a cohort of patients with DYRK1A haploinsufficiency has a higher prevalence of CAKUT (73% of those assessed), including kidney defects. By using <em>Xenopus laevis</em> as a model we determine that DYRK1A is essential for kidney development. Loss of <em>dyrk1a</em> in <em>Xenopus</em> leads to abnormal kidney formation, which can be rescued. Furthermore, I demonstrate that Dyrk1a perturbations lead to changes in β-catenin during embryogenesis. This dissertation reveals a new gene important for kidney development and disease and also has the potential to impact diagnostic patient treatment strategies for DYRK1A-syndrome patients.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2021

Authors dc:creator

• Blackburn, Alexandria
• <p><a href="https://orcid.org/0000-0003-2974-0339">https://orcid.org/0000-0003-2974-0339</a></p>

Contributors dc:contributor

• Rachel Miller
• Rebecca Berdeaux
• Vicki Huff

• Xenopus laevis
• nephron
• nephrogenesis
• CAKUT
• intellectual disability
• kidney
• exome sequencing
• Medicine and Health Sciences

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1068

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2125