The genetic basis of adrenal gland weight and structure in BXD recombinant inbred mice

Abstract

Adrenal gland function is mediated through secreted hormones, which play a vital role in the autonomic and hypothalamic-pituitary-adrenal (HPA)-axis-mediated stress response. The genetic underpinnings of the stress response can be approached using a quantitative trait locus (QTL) analysis. This method has been used to investigate genomic regions associated with variation in complex phenotypes, but it has not been used to explore the structure of the adrenal. We used QTL analyses to identify candidate genes underlying adrenal weight and adrenal cortical zone and medulla widths. We used 64 BXD recombinant inbred (RI) strains of mice (n = 528) and 2 parental strains (C57BL/6J and DBA/2J; n = 20) to measure adrenal weights and adrenal zone widths. For adrenal weight, we found significant QTLs on chromosome 3 for females (Fawq1) and Chr 4 for males (Mawq1) and suggestive QTLs on Chrs 1, 3, 10, and 14 for females and Chrs 2, 4, 10, 17, and X for males. We identified a significant QTL on Chr 10 (Mawdq1) and a suggestive QTL on Chr 13 for male adrenal total width. For male adrenal medulla width, we found a significant QTL on Chr 5 (Mmwdq1) and a suggestive QTL on Chr 1. We also identified significant QTLs on Chrs 10 (Mxwdq1) and 14 (Mxwdq2) for male X-zone width. There are 113 genes that mapped within the significant QTL intervals, and we identified 4 candidate genes associated with adrenal structure and/or function. In summary, this study is an important first step for detecting genetic factors influencing the structure of the adrenal component of the HPA axis using QTL analyses, which may relate to adrenal function and provide further insights into elucidating genes critical for stress-related phenotypes.

Expression and localization of pChAT as a novel method to study cholinergic innervation of rat adrenal gland

“…This was in agreement with what is reported in many animal species including rat (Rosol et al, 2001;Wan Ezumi et al, 2007) and mouse (Di Curzio and Goldowitz, 2011;Monfared et al, 2014). Although physiological studies have shown that the secretion of adrenal chromaffin cell is mediated by cholinergic agonists (Douglas and Poisner, 1965;Unger and Philips, 1983;De Diego, 2010), attempts to develop immunohistochemical markers for the identification of cholinergic neurons have presented several difficulties.…”

“…It plays a vital role in both the acute and the prolonged mammalian stress responses (Di Curzio and Goldowitz, 2011). In all adult mammals, the adrenal gland comprises the adrenal medulla and three layers of the adrenal cortex that surround the medulla (Deschepper et al, 2004).…”

“…In all adult mammals, the adrenal gland comprises the adrenal medulla and three layers of the adrenal cortex that surround the medulla (Deschepper et al, 2004). These cortical regions include the Zona glomerulosa, Zona fasciculata and Zona reticularis (Di Curzio and Goldowitz, 2011). The adrenal medulla comprises two types of chromaffin cells, adrenaline (epinephrine) and noradrenaline (nor-epinephrine) cells.…”

The agonistic adrenal: melatonin elicits female aggression via regulation of adrenal androgens

“…(e) Adrenal morphology and total steroid content Adrenal glands were histologically processed using a haematoxylin and eosin (H&E) stain via previously described methods [37]. The area encompassed by each cortical layer (i.e.…”

Analyses of differentially expressed genes after exposure to acute stress, acute ethanol, or a combination of both in mice

“…BXD RI mice have been used in quantitative trait locus (QTL) analyses and have been instrumental in identifying relevant chromosomal loci involved in ethanol and stress responses as well as potential candidate genes that underlie these QTLs (Mulligan et al, 2011, 2012, 2006; Belknap & Atkins, 2001; Buck, Metten, Belknap, & Crabbe, 1997; Cook et al, 2015; Hitzemann et al, 2004; Porcu et al, 2011; Wang et al, 2012; Weng, Symons, & Singh, 2009). Furthermore, BXD RI mice have been extensively evaluated for expression differences across a wide variety of brain regions and other organs (Boughter et al, 2012; Di Curzio & Goldowitz, 2011; Jellen et al, 2012; Lu et al, 2008, 2011; Mozhui, Lu, Armstrong, & Williams, 2012; Overall et al, 2009; Parker et al, 2014; Swaminathan, Lu, Williams, Lu, & Jablonski, 2013). The combination of all the data generated using BXD mice provides a powerful collection of resources that can be used to uncover genetic networks involved in complex phenotypes, making them an excellent model system.…”