Rtel1 in hypothalamic oxytocin neurons regulates oxytocin output and social behaviors in mice
- 1Songjiang Research Institute, Shanghai Jiao Tong University School of Medicine
Abstract
RTEL1, a DNA helicase that resolves G-quadruplexes to maintain telomere and genome stability, has emerged as a candidate autism spectrum disorder risk gene, but its neural functions remain unknown. Here, we show that Rtel1 haploinsufficiency in mice impairs social novelty and increases marble burying and anxiety-related behaviors without affecting locomotion or spatial learning. RTEL1 is expressed in oxytocin (OXT) neurons of the hypothalamic paraventricular nucleus, where Rtel1 haploinsufficiency reduces OXT abundance and blunts social-evoked OXT sensor responses. RTEL1 associates with a G-quadruplex-forming sequence near the Oxt transcription start site, and purified RTEL1 binds and unwinds this structure in an ATP-dependent manner. Rtel1 reduction in Oxt -lineage cells recapitulates the social and OXT phenotypes, whereas adult RTEL1 re-expression in paraventricular OXT neurons increases OXT abundance and ameliorates behavioral abnormalities. These findings uncover a non-telomeric function for RTEL1 linking promoter DNA structure to hypothalamic oxytocin output and social behavior.
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BibTeX
@misc{wang2026rtel1,
title = {{Rtel1 in hypothalamic oxytocin neurons regulates oxytocin output and social behaviors in mice}},
author = {J. Wang and X. Wang and Z. Qiu},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.10.750776},
url = {https://www.biorxiv.org/content/10.64898/2026.09.10.750776v1},
note = {Public domain},
}
RIS
TY - UNPB
TI - Rtel1 in hypothalamic oxytocin neurons regulates oxytocin output and social behaviors in mice
AU - J. Wang
AU - X. Wang
AU - Z. Qiu
PY - 2026
DA - 2026/09/10
PB - bioRxiv
DO - 10.64898/2026.09.10.750776
UR - https://www.biorxiv.org/content/10.64898/2026.09.10.750776v1
AB - RTEL1, a DNA helicase that resolves G-quadruplexes to maintain telomere and genome stability, has emerged as a candidate autism spectrum disorder risk gene, but its neural functions remain unknown. Here, we show that Rtel1 haploinsufficiency in mice impairs social novelty and increases marble burying and anxiety-related behaviors without affecting locomotion or spatial learning. RTEL1 is expressed in oxytocin (OXT) neurons of the hypothalamic paraventricular nucleus, where Rtel1 haploinsufficiency reduces OXT abundance and blunts social-evoked OXT sensor responses. RTEL1 associates with a G-quadruplex-forming sequence near the Oxt transcription start site, and purified RTEL1 binds and unwinds this structure in an ATP-dependent manner. Rtel1 reduction in Oxt -lineage cells recapitulates the social and OXT phenotypes, whereas adult RTEL1 re-expression in paraventricular OXT neurons increases OXT abundance and ameliorates behavioral abnormalities. These findings uncover a non-telomeric function for RTEL1 linking promoter DNA structure to hypothalamic oxytocin output and social behavior.
ER -