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by qwen3.7-flash, 2026-10-03
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This study investigates the function of the long noncoding RNA Dory, which exhibits sex-specific expression in the mouse hippocampus and cerebellum. Researchers found that deleting or knocking down Dory impairs spatial memory and balance specifically in female mice, while male performance remains unaffected. The authors note that this behavioral deficit correlates with differential gene and protein expression profiles in the hippocampus between sexes, despite no overt changes in brain morphology. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
Abstract
Large numbers of long noncoding RNAs (lncRNAs) exhibit region- or cell-specific expression and subcellular locations in the mammalian brain. We analyzed the expression and function of the mouse lncRNA 2700046G09Rik (also called Sgms1os1 ), which we have named Dory due to sex-specific disruption of spatial memory in rodent gene knockout and RNA knockdown. We show that Dory is predominantly expressed in a punctate pattern in nuclei of excitatory neurons in the hippocampus, and in both neuronal and non-neuronal cells in the cerebellum. We show by high resolution RNA sequencing that Dory brain transcripts are composed of 1-3 exons with multiple isoforms. Deletion of the constitutive first exon of Dory by CRISPR-Cas9 genome editing resulted in the impairment of spatial memory and some aspects of balance in female but not male mice. Dory -null mice presented without overt changes in brain morphology. Knockdown of the rat homolog of Dory in dorsal hippocampus using antisense oligonucleotides confirmed inhibition of spatial memory in females only. RNA sequencing and mass spectrometry revealed differential hippocampal gene and protein expression profiles, notably of prolactin, growth hormone and pro-opiomelanocortin, between male and female Dory knockout mice.
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Abstract
Large numbers of long noncoding RNAs (lncRNAs) exhibit region- or cell-specific expression and subcellular locations in the mammalian brain. We analyzed the expression and function of the mouse lncRNA 2700046G09Rik (also called Sgms1os1), which we have named Dory due to sex-specific disruption of spatial memory in rodent gene knockout and RNA knockdown. We show that Dory is predominantly expressed in a punctate pattern in nuclei of excitatory neurons in the hippocampus, and in both neuronal and non-neuronal cells in the cerebellum. We show by high resolution RNA sequencing that Dory brain transcripts are composed of 1-3 exons with multiple isoforms. Deletion of the constitutive first exon of Dory by CRISPR-Cas9 genome editing resulted in the impairment of spatial memory and some aspects of balance in female but not male mice. Dory-null mice presented without overt changes in brain morphology. Knockdown of the rat homolog of Dory in dorsal hippocampus using antisense oligonucleotides confirmed inhibition of spatial memory in females only. RNA sequencing and mass spectrometry revealed differential hippocampal gene and protein expression profiles, notably of prolactin, growth hormone and pro-opiomelanocortin, between male and female Dory knockout mice.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
K.C. and L.F. were missed in the author list after completion of rat knockdown studies. This revision updates the author list and contributions to reflect their input.
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