Yue Zhou

Publications (3)12.31 Total impact

• Article: The mutation in Chd7 causes misexpression of Bmp4 and developmental defects in telencephalic midline.

  Xuan Jiang, Yue Zhou, Li Xian, Weiqian Chen, Hanwei Wu, Xiang Gao
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  ABSTRACT: Mutations in chromosome-helicase-DNA-binding protein 7 (CHD7) are identified as the main cause for CHARGE syndrome (coloboma, heart anomaly, choanal atresia, retardation, genital and ear anomalies). Most patients (55% to 85%) with CHARGE syndrome display developmental defects in the central nervous system (CNS), of which pathology and molecular mechanisms remain unclear. In this study, we report a novel mutant mouse strain carrying a nonsense mutation, COA1, in exon4 of Chd7 gene. Chd7(COA1/+) mice phenocopied human CHARGE syndrome and displayed developmental defects in the telencephalic midline, including dilated third and lateral ventricles, reduced cerebral cortex, and corpus callosum crossing failure. Programed cell death in the telencephalic midline zone of Chd7(COA1/+) embryos was impaired, consistent with the incomplete telencephalic medial invagination in Chd7(COA1/+) embryos. Interestingly, expression of Bmp4, a signal well known to induce forebrain midline cell fate and apoptosis, was down-regulated and also expanded in the forebrain of Chd7(COA1/+) embryos. Furthermore, in vitro studies suggested that CHD7 may directly regulate Bmp4 expression by binding with an enhancer element downstream of the Bmp4 locus. These studies provide novel insight into pathogenesis of CNS anomalies in CHARGE syndrome.
  American Journal Of Pathology 05/2012; 181(2):626-41. · 4.89 Impact Factor
• Article: Gsdma3 mutation causes bulge stem cell depletion and alopecia mediated by skin inflammation.

  Yue Zhou, Xuan Jiang, Pengyu Gu, Weiqian Chen, Xuesi Zeng, Xiang Gao
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  ABSTRACT: Primary cicatricial alopecias (PCAs) are a group of permanent hair loss disorders, of which the pathogenesis is still poorly understood. The alopecia and excoriation (AE) mouse strain is a dominant mutant generated from ethyl nitrosourea mutagenesis. AE mice exhibit a progressive alopecia phenotype similar to that seen in PCAs, resulting from a point mutation in the gasdermin A3 gene. Mutant mice begin to show alopecia on the head from postnatal day 22 and experience complete hair loss by the age of 6 months, along with hyperkeratosis and catagen delay. The results of a histological examination showed that bulge stem cells in AE skin are gradually depleted, as indicated by decreased keratin 15 and CD34 expression, and reduced bromodeoxyuridine label-retaining cells in the AE bulge. In addition, AE mice display an inflammatory condition in the skin from postnatal day 7, including elevated tumor necrosis factor-α and monocyte chemotactic protein-1 mRNA levels and significantly increased macrophages and dendritic cell number. Immune privilege in the bulge was also compromised in AE skin. Consistently, after treatment with the immunosuppressive agent, cyclosporine A, immune privilege collapse, stem cell destruction, and alopecia phenotype of AE mice were all rescued. Collectively, our data demonstrate that immune-mediated destruction of bulge stem cells plays a crucial role in the pathogenesis of alopecia in AE mice, and this strain might be an interesting model for PCAs, especially for lichen planopilaris.
  American Journal Of Pathology 12/2011; 180(2):763-74. · 4.89 Impact Factor
• Article: Generation of Ppp2Ca and Ppp2Cb conditional null alleles in mouse.

  Pengyu Gu, Xin Qi, Yue Zhou, Yun Wang, Xiang Gao
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  ABSTRACT: Protein phosphatase 2A (PP2A) is one of the most abundant serine/threonine phosphatases, with a critical role in embryonic development and human disease. There are two isoforms of the catalytic subunit of PP2A, Ppp2ca and Ppp2cb. Null mutation of Ppp2ca leads to early embryonic lethality at E6.5, hindering functional study of PP2A beyond this stage. We generated conditional null alleles of Ppp2ca and Ppp2cb by flanking with loxP sites exons 3 to 5 of Ppp2ca and exon 3 of Ppp2cb. Ppp2ca(fl/fl) mice did not display any visible phenotype. Homozygous mutants in which Cre-mediated excision resulted in global deletion of Ppp2ca displayed embryonic lethality and developmental defects similar to those previously reported. Ppp2cb(Δ/Δ) mice generated by the same strategy did not display any obvious morphological or physiological defects. These mouse strains can serve as important genetic tools to study the roles of PP2A during development and disease in a spatial- or temporal-specific manner.
  genesis 10/2011; 50(5):429-36. · 2.53 Impact Factor