Deregulation of ZPR1 causes respiratory failure in spinal muscular atrophy

被引：14

作者：

Genabai, Naresh K. ^{[1
,2
]}

Kannan, Annapoorna ^{[1
,2
]}

Ahmad, Saif ^{[1
,2
]}

Jiang, Xiaoting ^{[1
,2
,3
]}

Bhatia, Kanchan ^{[1
,2
]}

Gangwani, Laxman ^{[1
,2
,3
]}

机构：

[1] Texas Tech Univ, Hlth Sci Ctr, Ctr Emphasis Neurosci, El Paso, TX 79905 USA

[2] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Dept Biomed Sci, El Paso, TX 79905 USA

[3] Texas Tech Univ, Hlth Sci Ctr, Grad Sch Biomed Sci, El Paso, TX 79905 USA

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

基金：

美国国家卫生研究院;

关键词：

FINGER PROTEIN ZPR1; HOMEOBOX GENE; SMN PROTEIN; SURVIVAL; MICE; DEFICIENCY; NETWORK; COMPLEX; LEVEL; HOXA5;

D O I：

10.1038/s41598-017-07603-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Spinal muscular atrophy (SMA) is caused by the low levels of survival motor neuron (SMN) protein and is characterized by motor neuron degeneration and muscle atrophy. Respiratory failure causes death in SMA but the underlying molecular mechanism is unknown. The zinc finger protein ZPR1 interacts with SMN. ZPR1 is down regulated in SMA patients. We report that ZPR1 functions downstream of SMN to regulate HoxA5 levels in phrenic motor neurons that control respiration. Spatiotemporal inactivation of Zpr1 gene in motor neurons down-regulates HoxA5 and causes defects in the function of phrenic motor neurons that results in respiratory failure and perinatal lethality in mice. Modulation in ZPR1 levels directly correlates and influences levels of HoxA5 transcription. In SMA mice, SMN-deficiency causes down-regulation of ZPR1 and HoxA5 that result in degeneration of phrenic motor neurons. Identification of ZPR1 and HoxA5 as potential targets provides a paradigm for developing strategies to treat respiratory distress in SMA.

引用

页数：17

共 48 条

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