Paediatrics Publications

Document Type

Article

Publication Date

6-7-2018

Journal

Aging (Albany NY)

Volume

10

Issue

6

First Page

1223

Last Page

1238

URL with Digital Object Identifier

https://doi.org/10.18632/aging.101462

Abstract

ATRX is an ATP‐dependent chromatin remodeler required for the maintenance of genomic integrity. We previously reported that conditional Atrx ablation in the mouse embryonic forebrain and anterior pituitary using the Foxg1cre driver causes reduced health and lifespan. In these mice, premature aging‐like phenotypes were accompanied by low circulating levels of insulin‐like growth factor 1 (IGF‐1) and thyroxine (T4), hormones that maintain stem cell pools and normal metabolic profiles, respectively. Based on emerging evidence that T4 stimulates expression of IGF‐1 in pre‐pubertal mice, we tested whether T4 supplementation in Atrx Foxg1cre mice could restore IGF‐1 levels and ameliorate premature aging‐like phenotypes. Despite restoration of normal serum T4 levels, we did not observe improvements in circulating IGF‐1. In the liver, thyroid hormone target genes were differentially affected upon T4 treatment, with Igf1 and several other thyroid hormone responsive genes failing to recover normal expression levels. These findings hinted at Cre‐mediated Atrx inactivation in the liver of Atrx Foxg1cre mice, which we confirmed. We conclude that the phenotypes observed in the Atrx Foxg1cre mice can be explained in part by a role of ATRX in the liver to promote T4‐mediated Igf1 expression, thus explaining the inefficacy of T4 therapy observed in this study.

Notes

Article originally published at Aging, Vol. 10(6)

https://doi.org/10.18632/aging.101462

© 2018 The author(s)

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

Find in your library

Included in

Pediatrics Commons

Share

COinS