The Transcriptomics of the Hypothalamic-Kidney Axis in a Desert Rodent

Abstract

Osmoregulation is critical to all mammals. The actions of the hypothalamus (specifically the Supraoptic Nucleus (SON)) and the kidney are essential in maintaining the body’s water balance. The discovery of Arginine-Vasopressin (AVP), its expression in the SON, and its water conserving effect on the kidney led to transcriptomic studies of these tissues during water restriction in model organisms. These large datasets pointed to understudied genes. Building on previous datasets, this thesis aims to characterise the response to water restriction and rehydration in a model that is specifically adapted to deal with these environmental stressors. Jaculus jaculus (aka Jerboa) lives in the desert habitat of North Africa and the Arabian Peninsula. The Jerboa was seen as an ideal model to investigate efficient osmoregulation in physiological studies in the 1970s and ’80s. However, the technology was not available to look at tissue wide gene expression then. Here, the Jerboa’s physiological response to chronic water restriction (10/11 days) and rehydration is first characterised to show canonical changes in body weight, plasma sodium, and the release of AVP from the Posterior Pituitary (PP). The gene expression profile of the whole kidney was then elucidated, showing large changes in the expression of solute channels, an increase in translation during rehydration, and Transforming Growth Factor β (TGF-b) receptor antagonism during dehydration. The SON had fewer Differentially Expressed Genes (DEGs) between the experimental groups but did show changed expression of AVP and other established genes known to be active in osmoregulation. Understanding how these desert derived datasets fit
into the wider data collected from other xeric and mesic mammals is important. To that end, a cross species comparison showed a select few genes that are differentially expressed across all species in the SON or kidney. This exploratory work generates a list of candidate genes that should be investgiated further to establish their functional role in osmoregulation.

Date of Award	23 Jan 2024
Original language	English
Awarding Institution	University of Bristol
Supervisor	Michael P Greenwood (Supervisor) & David Murphy (Supervisor)