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The genetic basis for adrenal gland structure : a focus on the stress response Di Curzio, Domenico Luciano


Adrenal gland function is mediated through secreted hormones, and these hormones play a vital role in the autonomic and HPA-axis mediated stress response. Stress is a complex phenomenon, and the genetic underpinnings of it 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 in the mouse CNS and anatomical variation in organ weights. However, it has not been previously used to explore the structure of the adrenal gland. In this study, we used QTL analyses to identify candidate genes underlying adrenal weight and adrenal cortical zones and medulla widths. We used 64 BXD recombinant inbred (RI) strains of mice (n = 571) and 2 parental strains (C57BL/6J and DBA/2J; n = 20) to measure adrenal weights. These 64 BXD RI strains and the progenitor strains were then examined to measure adrenal zone widths. We performed QTL linkage analysis (with WebQTL) to identify QTLs associated with adrenal weight. We found significant QTLs on chromosome 3 for females and Chr 4 for males 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 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 and a suggestive QTL on Chr 1. In addition, we identified significant QTLs on Chrs 10 and 14 for male X-zone width. Finally, there are 114 genes that mapped within the significant QTL intervals, of which we identified 5 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 analysis, which may relate to adrenal function and provide further insights into elucidating genes critical for stress-related phenotypes.

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