查看“PAX3”的源代码

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            <strong>PAX3</strong> (Paired Box 3) 是配对盒转录因子家族的关键成员，在胚胎发育中作为“核心架构师”，调控<strong>[[神经嵴细胞]]</strong>（生成黑色素细胞、神经节、面部骨骼）和<strong>[[体节]]</strong>（生成骨骼肌）的迁移与分化。PAX3 的功能剂量高度敏感：其单倍体剂量不足（Haploinsufficiency）导致 <strong>[[瓦登伯格综合征]]</strong>（听力丧失与色素异常）；而其发生染色体易位 <strong>t(2;13)</strong> 则产生强效致癌融合蛋白 <strong>[[PAX3-FOXO1]]</strong>，驱动高侵袭性的 <strong>[[腺泡状横纹肌肉瘤]]</strong>。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">PAX3 档案</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Developmental Master Regulator</div>
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                        结构域:<br>Paired Box (DNA)<br>Homeobox (DNA)
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">功能：神经/肌肉/色素发育</div>
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                <tr><th style="text-align: left; padding: 10px 12px; border-bottom: 1px solid #f1f5f9; background-color: #f8fafc;">[[Entrez]] ID</th><td style="padding: 10px 12px; border-bottom: 1px solid #f1f5f9;">5077</td></tr>
                <tr><th style="text-align: left; padding: 10px 12px; border-bottom: 1px solid #f1f5f9; background-color: #f8fafc;">[[HGNC]] 符号</th><td style="padding: 10px 12px; border-bottom: 1px solid #f1f5f9;">PAX3</td></tr>
                <tr><th style="text-align: left; padding: 10px 12px; border-bottom: 1px solid #f1f5f9; background-color: #f8fafc;">[[UniProt]]</th><td style="padding: 10px 12px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">P23760</td></tr>
                <tr><th style="text-align: left; padding: 10px 12px; border-bottom: 1px solid #f1f5f9; background-color: #f8fafc;">染色体定位</th><td style="padding: 10px 12px; border-bottom: 1px solid #f1f5f9;">2q36.1</td></tr>
                <tr><th style="text-align: left; padding: 10px 12px; border-bottom: 1px solid #f1f5f9; background-color: #f8fafc;">分子量</th><td style="padding: 10px 12px; border-bottom: 1px solid #f1f5f9;">~53 kDa</td></tr>
                <tr><th style="text-align: left; padding: 10px 12px; background-color: #f8fafc;">临床综合征</th><td style="padding: 10px 12px; color: #1e40af; font-weight: bold;">Waardenburg Syn I/III</td></tr>
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        PAX3 通过结合下游靶基因的启动子或增强子区域，协调多个谱系的发育程序：
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        <li style="margin-bottom: 12px;"><strong>黑色素细胞生成：</strong> PAX3 直接反式激活 <strong>[[MITF]]</strong> (Microphthalmia-associated transcription factor)，这是黑色素细胞生存和色素合成的主控基因。PAX3 缺失会导致内耳血管纹和皮肤黑色素细胞缺如，引起耳聋和白斑。</li>
        <li style="margin-bottom: 12px;"><strong>肢体肌肉形成：</strong> 在体节发育中，PAX3 诱导 <strong>[[c-Met]]</strong> 受体的表达，使肌祖细胞能够响应 HGF 信号，从体节迁移至肢芽，形成四肢肌肉。</li>
        <li style="margin-bottom: 12px;"><strong>神经管闭合：</strong> PAX3 抑制 <strong>[[p53]]</strong> 介导的凋亡，确保神经管形成过程中的细胞存活。功能丧失可能导致神经管缺陷（如脊柱裂）。</li>
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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a;">病理状态</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">相关疾病</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床特征</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">功能丧失 (LOF)<br><span style="font-size:0.8em; color:#64748b;">点突变/缺失</span></td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">瓦登伯格综合征 1型/3型 (Waardenburg)</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">感音神经性耳聋、虹膜异色、额前白发、内眦赘皮（Dystopia canthorum）。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">功能获得 (GOF)<br><span style="font-size:0.8em; color:#64748b;">染色体易位</span></td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">腺泡状横纹肌肉瘤 (ARMS)</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>[[PAX3-FOXO1]]</strong> 融合蛋白充当超级激活剂，阻断细胞分化，驱动肿瘤快速生长。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">多效性缺陷</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">颅面-耳聋-手综合征</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">罕见表型，伴有严重的鼻部和手部肌肉骨骼发育不全。</td>
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        <li style="margin-bottom: 12px;"><strong>肉瘤靶向：</strong> 针对 PAX3-FOXO1 融合蛋白，目前的策略集中在破坏其转录复合物的稳定性（如 <strong>[[BET 抑制剂]]</strong>）或阻断其下游关键效应因子（如 <strong>[[FGFR4]]</strong> 抑制剂）。</li>
        <li style="margin-bottom: 12px;"><strong>干细胞诱导：</strong> 利用 PAX3 的过表达，研究人员可在体外将诱导多能干细胞 (iPSCs) 高效重编程为肌源性祖细胞，用于治疗肌营养不良的细胞疗法研究。</li>
        <li style="margin-bottom: 12px;"><strong>色素再生：</strong> 理解 PAX3-MITF 轴的调控机制，为治疗白癜风等色素脱失性疾病提供了潜在的药物筛选靶点。</li>
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            [[神经嵴 (Neural Crest)]] • [[瓦登伯格综合征]] • [[PAX3-FOXO1]] • [[MITF]] • [[c-Met]]
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        <span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献 [Academic Review]</span>
        
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            [1] <strong>Tassabehji M, et al. (1992).</strong> <em>Waardenburg syndrome type 1 is caused by mutations in the PAX3 gene.</em> <strong>Nature Genetics</strong>. 2(1):26-30.<br>
            <span style="color: #475569;">[遗传学突破]：首次将 PAX3 鉴定为人类遗传性耳聋和色素异常疾病的致病基因。</span>
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            [2] <strong>Barr FG, et al. (1993).</strong> <em>Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma.</em> <strong>Nature Genetics</strong>. 3(2):113-117.<br>
            <span style="color: #475569;">[肿瘤学突破]：发现 t(2;13) 易位导致 PAX3 基因重排，开启了肉瘤分子诊断的时代。</span>
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            [3] <strong>Buckingham M, Relaix F. (2007).</strong> <em>The role of Pax genes in the development of tissues and organs: Pax3 and Pax7 regulate muscle progenitor cell functions.</em> <strong>Annual Review of Cell and Developmental Biology</strong>. 23:645-673.<br>
            <span style="color: #475569;">[综述]：系统阐述了 PAX3 在肌肉发育调控网络中的核心地位。</span>
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            PAX3 · 知识图谱
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right;">下游靶点</td>
                <td style="padding: 10px 15px; color: #334155;">[[MITF]] (色素) • [[c-Met]] (迁移) • [[MyoD]] (成肌)</td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right;">家族成员</td>
                <td style="padding: 10px 15px; color: #334155;">[[PAX7]] (肌肉干细胞) • [[PAX6]] (眼发育)</td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right;">病理关联</td>
                <td style="padding: 10px 15px; color: #334155;">[[神经性耳聋]] • [[横纹肌肉瘤]] • [[白化病]]</td>
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