曲1 拯救了杜申肌肉缩现象
Natassia M Vieira1, Ingegerd Elvers2, Matthew S Alexander3
1The Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics and Genetics, Harvard Medical School, Boston, MA 02115, USA; Human Genome and Stem Cell Center, Biosciences Institute, University of São Paulo, São Paulo 05508-090, Brazil.
Cell
|November 20, 2015
概括
轻度受影响的黄金猎犬肌肉发育不良的狗表现出Jagged1基因表达的增加. 这表明Jagged1可能是杜申肌力发育不良的治疗点,提供了无素治疗方法.
科学领域:
- 遗传学
- 分子生物学
- 动物模型
背景情况:
- 杜申肌肉发育不良 (DMD) 是一种严重的遗传性疾病,没有治愈的方法,其特征是缺乏肌肉发育不良.
- 目前的DMD疗法在恢复失色蛋白表达方面具有有限的有效性.
- 在DMD中失调的信号通路是潜在的治疗点.
研究的目的:
- 调查黄金猎犬肌肉缩症 (GRMD) 轻度杜申肌肉缩症表型的遗传和分子基础.
- 为了确定杜申肌力发育不良的潜在治疗点,独立于肌力发育不良的恢复.
主要方法:
- 联系分析
- 全基因组测序
- 转录组分析
- 具有轻度和重度表型的GRMD狗和对照动物的比较分析
主要成果:
- 鉴定出两只特殊的GRMD狗具有轻度的表型,功能肌肉和正常寿命,尽管完全没有缩蛋白.
- 在轻度受影响的狗中发现了显著增加的Jagged1基因表达.
- 在功能分析中证明Jagged1的过度表达改善了变质表型.
结论:
- 增加的Jagged1基因表达与轻度的杜申肌肉衰竭表型有关.
- Jagged1是杜申肌力发育不良的潜在治疗点,提供了新的无素治疗策略.
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