NELF knockout is associated with impaired pubertal development and subfertility.
NELF knockout is associated with impaired pubertal development and subfertility.
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NELF敲除与青春期发育和差异性受损有关。
DOI：
10.1016/j.mce.2015.02.015
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发表时间：
2015-05-15
影响因子：
4.1
通讯作者：
Layman, Lawrence C.
中科院分区：
文献类型：
--
作者：
Quaynor, Samuel D.;Ko, Eun Kyung;Chorich, Lynn P.;Sullivan, Megan E.;Demir, Durkadin;Waller, Jennifer L.;Kim, Hyung-Goo;Cameron, Richard S.;Layman, Lawrence C.
青春期和生殖需要由促性腺激素释放激素（GnRH）神经元控制的下丘脑-垂体-性腺轴的适当信号传导，这些神经元出现在嗅觉基板区域并沿着嗅觉轴突迁移到下丘脑。对 GnRH 神经元规格、迁移和功能产生不利影响的因素会导致青春期延迟和不孕。鼻胚胎黄体生成素释放因子（NELF）主要是一种核蛋白。 NELF 突变已在低促性腺激素性性腺功能减退症患者中得到证实，但双等位基因突变很罕见，杂合 NELF 突变通常与另一个基因的突变共存。我们之前对永生化 GnRH 神经元的研究支持 NELF 在 GnRH 神经元迁移中的作用。为了更好地了解 NELF 的生理学，建立了纯合 Nelf 敲除 (KO) 小鼠模型。我们的研究结果表明，雌性 Nelf KO 小鼠阴道开放延迟，但首次发情时间没有延迟，子宫重量减轻，GnRH 神经元数量减少。相比之下，雄性小鼠在青春期表现正常。两性小鼠的生育能力均受损，表现为平均产仔数减少。这些数据支持NELF具有重要的生殖功能。 KO 小鼠比预期更温和的表型也重现了人类表型，因为杂合 NELF 突变通常需要第二个基因发生额外突变才能导致低促性腺激素性性腺功能减退症。
Puberty and reproduction require proper signaling of the hypothalamic-pituitary-gonadal axis controlled by gonadotropin-releasing hormone (GnRH) neurons, which arise in the olfactory placode region and migrate along olfactory axons to the hypothalamus. Factors adversely affecting GnRH neuron specification, migration, and function lead to delayed puberty and infertility. Nasal embryonic luteinizing hormone-releasing factor (NELF) is a predominantly nuclear protein. NELF mutations have been demonstrated in patients with hypogonadotropic hypogonadism, but biallelic mutations are rare and heterozygous NELF mutations typically co-exist with mutations in another gene. Our previous studies in immortalized GnRH neurons supported a role for NELF in GnRH neuron migration. To better understand the physiology of NELF, a homozygous Nelf knockout (KO) mouse model was generated. Our findings indicate that female Nelf KO mice have delayed vaginal opening but no delay in time to first estrus, decreased uterine weight, and reduced GnRH neuron number. In contrast, male mice were normal at puberty. Both sexes of mice had impaired fertility manifested as reduced mean litter size. These data support that NELF has important reproductive functions. The milder than expected phenotype of KO mice also recapitulates the human phenotype since heterozygous NELF mutations usually require an additional mutation in a second gene to result in hypogonadotropic hypogonadism.
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影响因子：
9.8
作者：
Dieterich, Daniela C.;Karpova, Anna;Mikhaylova, Marina;Zdobnova, Irina;Koenig, Imbritt;Landwehr, Marco;Kreutz, Martin;Smalla, Karl-Heinz;Richter, Karin;Landgraf, Peter;Reissner, Carsten;Boeckers, Tobias M.;Zuschratter, Werner;Spilker, Christina;Seidenbecher, Constanze I.;Garner, Craig C.;Gundelfinger, Eckart D.;Kreutz, Michael R.
通讯作者：
Kreutz, Michael R.
影响因子：
4.5
作者：
Hanchate NK;Giacobini P;Lhuillier P;Parkash J;Espy C;Fouveaut C;Leroy C;Baron S;Campagne C;Vanacker C;Collier F;Cruaud C;Meyer V;García-Piñero A;Dewailly D;Cortet-Rudelli C;Gersak K;Metz C;Chabrier G;Pugeat M;Young J;Hardelin JP;Prevot V;Dodé C
通讯作者：
Dodé C
DOI：
10.1523/jneurosci.1688-10.2011
发表时间：
2011-01-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Larder R;Clark DD;Miller NL;Mellon PL
通讯作者：
Mellon PL
影响因子：
3.5
作者：
Bosman, EA;Penn, AC;Steel, KP
通讯作者：
Steel, KP
影响因子：
3.5
作者：
Cariboni, Anna;Davidson, Kathryn;Ruhrberg, Christiana
通讯作者：
Ruhrberg, Christiana