Normal X-inactivation mosaicism in corneas of heterozygous FlnaDilp2/+ female mice--a model of human filamin A (FLNA) diseases.
Normal X-inactivation mosaicism in corneas of heterozygous FlnaDilp2/+ female mice--a model of human filamin A (FLNA) diseases.
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DOI：
10.1186/1756-0500-5-122
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发表时间：
2012-02-27
影响因子：
1.8
通讯作者：
West JD
中科院分区：
文献类型：
--
作者：
Douvaras P;Liu W;Mort RL;McKie L;West KM;Cross SH;Morley SD;West JD
小鼠角膜上皮维持的一些异常可以通过它们在 X 染色体失活嵌合体和嵌合体中产生的非典型嵌合模式来识别。人类 FLNA/+ 女性，X 连锁细丝蛋白 A 基因 (FLNA) 突变杂合，表现出一系列疾病，并且 X 失活镶嵌有时在数量上不平衡。 FlnaDilp2/+ 小鼠是 X 连锁细丝蛋白 A (Flna) 无义突变杂合子，具有不同的眼睛、骨骼和其他异常，但尚未研究 X 失活镶嵌现象。本研究的目的是确定 FlnaDilp2/+ 小鼠角膜上皮中的 X 失活镶嵌是否受到任何可能预测角膜上皮维护异常的影响。使用β-半乳糖苷酶组织化学染色，在 FlnaDilp2/+ 的角膜上皮和对照组织（肝脏）以及野生型 (WT) 雌性 X 失活镶嵌体（X 连锁 LacZ 报告基因 H253 转基因半合子）中研究了 X 染色体失活镶嵌现象。 FlnaDilp2/+ 和 WT X-失活镶嵌体的角膜上皮显示出相似的放射状条纹图案，这意味着 FlnaDilp2/+ 角膜中的上皮细胞运动没有被破坏。校正后的条纹数量随着总体年龄的增长而下降（但对于任一基因型而言均不显着），这与之前的报告一致，表明干细胞功能与年龄有关。与WT X失活嵌合体相比，FlnaDilp2/+中校正的条纹数量没有减少，并且FlnaDilp2/+的角膜上皮或肝脏中的嵌合体并不比野生型Flna+/+ X失活嵌合体显着更不平衡。镶嵌分析发现小鼠 FlnaDilp2 突变对角膜上皮维持或角膜上皮或肝脏中 X 失活镶嵌的平衡没有重大影响。
Some abnormalities of mouse corneal epithelial maintenance can be identified by the atypical mosaic patterns they produce in X-chromosome inactivation mosaics and chimeras. Human FLNA/+ females, heterozygous for X-linked, filamin A gene (FLNA) mutations, display a range of disorders and X-inactivation mosaicism is sometimes quantitatively unbalanced. FlnaDilp2/+ mice, heterozygous for an X-linked filamin A (Flna) nonsense mutation have variable eye, skeletal and other abnormalities, but X-inactivation mosaicism has not been investigated. The aim of this study was to determine whether X-inactivation mosaicism in the corneal epithelia of FlnaDilp2/+ mice was affected in any way that might predict abnormal corneal epithelial maintenance. X-chromosome inactivation mosaicism was studied in the corneal epithelium and a control tissue (liver) of FlnaDilp2/+ and wild-type (WT) female X-inactivation mosaics, hemizygous for the X-linked, LacZ reporter H253 transgene, using β-galactosidase histochemical staining. The corneal epithelia of FlnaDilp2/+ and WT X-inactivation mosaics showed similar radial, striped patterns, implying epithelial cell movement was not disrupted in FlnaDilp2/+ corneas. Corrected stripe numbers declined with age overall (but not significantly for either genotype individually), consistent with previous reports suggesting an age-related reduction in stem cell function. Corrected stripe numbers were not reduced in FlnaDilp2/+ compared with WT X-inactivation mosaics and mosaicism was not significantly more unbalanced in the corneal epithelia or livers of FlnaDilp2/+ than wild-type Flna+/+ X-inactivation mosaics. Mosaic analysis identified no major effect of the mouse FlnaDilp2 mutation on corneal epithelial maintenance or the balance of X-inactivation mosaicism in the corneal epithelium or liver.