Defects in vestibular sensory epithelia and innervation in mice with loss of chd7 function:: Implications for human CHARGE syndrome
Defects in vestibular sensory epithelia and innervation in mice with loss of chd7 function:: Implications for human CHARGE syndrome
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DOI：
10.1002/cne.21460
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发表时间：
2007-10-10
影响因子：
2.5
通讯作者：
Martin, Donna M.
中科院分区：
文献类型：
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作者：
Adams, Meredith E.;Hurd, Elizabeth A.;Martin, Donna M.
CHD 7是CHARGE综合征中突变的染色体结构域基因，CHARGE综合征是一种以眼缺损、心脏缺陷、软骨闭锁、生长发育迟缓、生殖器发育不全和耳缺陷（包括耳聋和半规管发育不全）为特征的多发性异常病症。Chd 7杂合子缺陷小鼠具有绕圈行为和半规管缺陷，是探索CHARGE特征发病机制的良好动物模型。内耳前庭缺陷的特点是在杂合子Chd 7缺陷的胚胎和出生后早期的小鼠，但目前尚不清楚是否前庭缺陷持续整个成年期Chd 7缺陷的小鼠或前庭感觉上皮细胞及其相关的神经支配和功能是完整的。在这里，我们描述了一个详细的分析内耳前庭结构的成熟小鼠是杂合子的Chd 7缺陷，基因捕获等位基因（Chd 7（Gt/+））。Chd 7（Gt/+）小鼠显示可变的不对称的外侧和后半规管畸形，以及前庭感觉上皮神经支配的缺陷，尽管在靶器官中存在完整的毛细胞。这些观察结果对于理解人类CHD 7突变的临床表现和设计治疗内耳前庭功能障碍的疗法具有重要的功能意义。
CHD7 is a chromodomain gene mutated in CHARGE syndrome, a multiple anomaly condition characterized by ocular coloboma, heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, and ear defects including deafness and semicircular canal dysgenesis. Mice with heterozygous Chd7 deficiency have circling behavior and semicircular canal defects and are an excellent animal model for exploring the pathogenesis of CHARGE features. Inner ear vestibular defects have been characterized in heterozygous Chd7-deficient embryos and early postnatal mice, but it is not known whether vestibular defects persist throughout adulthood in Chd7-deficient mice or whether the vestibular sensory epithelia and their associated innervation and function are intact. Here we describe a detailed analysis of inner ear vestibular structures in mature mice that are heterozygous for a Chd7-deficient, gene-trapped allele (Chd7(Gt/+)). Chd7(Gt/+) mice display variable asymmetric lateral and posterior semicircular canal malformations, as well as defects in vestibular sensory epithelial innervation despite the presence of intact hair cells in the target organs. These observations have important functional implications for understanding the clinical manifestations of CHD7 mutations in humans and for designing therapies to treat inner ear vestibular dysfunction.