数据日期 2026-10-29 · 生成时间 2026-10-29 06:03
研究问题
However, while the phenotype resulting from the total loss of LMD-3 is well-defined, the biological consequences of clinical missense mutations, such as the POI-associated W804C mutation identified in the human NCOA7 TLDc domain [19], remain to be elucidated in vivo.
方法
To ensure synchronized development for experiments, gravid adults were treated with a standard bleaching solution to harvest eggs.；Cross-fertilization assay To assess sperm functionality, cross-fertilization assays were conducted utilizing the spermless fem-1(hc17) mutant strain.；Subsequently, 1.2 μg of RNA was reverse-transcribed into cDNA using the HiScript III 1st Strand cDNA Synthesis Kit (+ gDNA wiper) (Vazyme, R312-01). qRT-PCR was conducted on an ABI QuantStudio 1 system (Thermo Fisher Scientific) utilizing ChamQ SYBR Color qPCR Master Mix (Vazyme, Q411-02).；Body length (head-to-tail dis- tance) was calculated using Image View software, with a minimum of 22 animals analyzed per experimental cohort.
核心结论
Despite the relatively low 26.46% overall amino acid sequence identity between LMD-3 and human NCOA7 [25], the func- tional domains and critical motifs are remarkably homologous (S1 Fig in S1 File).；Our analysis revealed a significant reproductive deficit: the mutant strain exhibited an approximate 15% reduction in total progeny output compared to wild-type animals (Fig 2A, 2B; S2A and S2B Fig in S1 File).；We quantified both egg-laying and hatching rates, revealing that lmd-3W690C mutants laid 14.94% fewer eggs than wild-type controls (S2C Fig in S1 File). ‖ 结论：Our previous work established LMD-3 as a critical regulator of reproductive capacity in C. elegans [24].
局限
Nevertheless, our model captures conserved core mechanisms of lysosomal collapse, offering metabolic insights that warrant mammalian validation.
对本项目的价值
★★★★☆ 营养感知与自噬轴决定"干预窗口 + 剂量方案"，是组合疗法的时间锚。命中核心 蛋白稳态/自噬；最大样本量约 200。
全文来源
PLOS OA PDF（正文 77,116 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：A premature ovarian insufficiency-associated LMD-3 point mutation impairs protein stability and causes autophagic-lysosomal dysfunction in Caenorhabditis elegans.
- 期刊与标识：PLoS One · PMID 42945204 · DOI 10.1371/journal.pone.0361215**
A 级证据分级：A 级（同行评议人体研究）
本文属人体研究证据，但需注意：观察性或小样本干预的结论不等于已证实临床获益；效应量与长期安全性仍需更大规模、更长随访的试验验证。
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