Language
English
Publication Date
12-15-2025
Journal
Communications Biology
DOI
10.1038/s42003-025-09322-y
PMID
41398470
PMCID
PMC12800023
PubMedCentral® Posted Date
12-15-2025
PubMedCentral® Full Text Version
Post-print
Abstract
The novel long non-coding RNA (lncRNA) Leat1 is extraordinarily conserved in both its location (syntenic with EfnB2, an essential gene in anogenital patterning) and sequence. Here we show that Leat1 is upregulated following the production of testosterone from the developing testis in mice and interacts with EfnB2, positively regulating its expression. Leat1 expression is suppressed by estrogen, which in turn suppresses the expression of EfnB2. Moreover, the loss of Leat1 leads to reduced EfnB2, resulting in a severe hypospadias phenotype. The human LEAT1 gene is also co-expressed with EFNB2 in the developing human penis, suggesting a conserved function for this gene in urethral closure. Together our data identify Leat1 as a novel molecular regulator of urethral closure and implicate it as a target of endocrine disruption in the etiology of hypospadias.
Keywords
Male, RNA, Long Noncoding, Animals, Mice, Humans, Hypospadias, Testosterone, Gene Expression Regulation, Developmental, Urethra, Penis, Testis, Urogenital System
Published Open-Access
yes
Recommended Citation
Mattiske, Deidre; Bernard, Pascal; Gradie, Paul E; et al., "A Long Non-coding RNA Leat1 Mediates the Hormone Responsiveness of EfnB2 During Male Urogenital Development" (2025). Faculty, Staff and Students Publications. 6465.
https://digitalcommons.library.tmc.edu/baylor_docs/6465