SOX14 is a candidate gene for limb defects associated with BPES and Möbius syndrome

Members of the SOX gene family encode proteins with homology to the HMG box DNA-binding domain of SRY, the Y-linked testis-determining gene. SOX genes are expressed during embryogenesis and are involved in the development of a wide range of different tissues. Mutations in SRY, SOX9 and SOX10 have been shown to be responsible for XY sex reversal, campomelic dysplasia and Waardenburg-Hirschsprung disease, respectively. It is likely that mutations in other SOX genes are responsible for a variety of human genetic diseases. SOX14 has been identified from a human genomic library and the mouse and chicken sequences obtained by polymerase chain reaction amplification. The SOX14 amino acid sequence is highly conserved across these species, suggesting an important role for this protein in vertebrate development. SOX14 is expressed in the neural tube and apical ectodermal ridge of the developing chicken limb. This is the only SOX gene known to be expressed in the apical ectodermal ridge, a structure that directs outgrowth of the embryonic limb bud. Human SOX14 is localised to a 1.15-Mb yeast artificial chromosome on chromosome 3q23, close to loci for BPES (blepharophimosis, ptosis, epicanthus inversus syndrome) and Mobius syndrome. Although SOX14 maps outside these loci, its expression pattern and chromosomal localisation suggest that it is a candidate gene for the limb defects frequently associated with these syndromes.     

FOXL2、SOX14及BPESC1 mRNA在小睑裂综合征患者眼睑组织中表达水平的研究

目的 研究小睑裂综合征（blephamphimosis—ptosis—epicanthusinversus syndrome,BPES）患者与正常人相比眼睑组织中FOX12、SOX14及BPESC13个基因mRNA的相对表达水平,探讨这3个基因与BPES的相关性,以及可能存在的发病机制。方法TRIzol法抽提眼睑组织总RNA,反转录为cDNA,应用实时荧光定量PCR技术分别检测15例BPES患者（A组）及15例正常人眼睑组织（B组）中FOXL2、SOX14和BPESClmRNA的表达水平,用两配对样本wilcoxon符号秩检验法和2-AAC,法分析两组数据及其差异。结果FOXL2、SOX14和BPESCI3个基因tuRNA的表达水平在A、B两组间的差异均具有统计学意义,P值均〈0．05。A、B两组间,FOXL2基因的△Ct之差（△△ct）,负秩与证秩的平均秩分别为6．00和8．50,SOX14基[天1的△△Ct负秩与正秩的平均秩分别为4．20和9．33,BPESC1基因的△△ct负秩与正秩的平均秩分别为8．23和6．50,可认为A组FOXL2基因和SOXl4基因的△ct值大于B组,BPESCI基因的△ct值小于B组,即A组的FOXL2基因和SOX14基因的表达水平低于B组,BPESCI基因表达水平高于B组。结论FOXL2、BPESC1及SOX14均与BPES具有一定相关性,FOXL2和SOX14的低表达以及BPESC1的高表达可能与BPES的发病相关。     

赤链蛇Sox基因的克隆及序列分析

参照人SRY基因HMG-box保守区的序列,设计一对兼并引物,采用PCR技术扩增了赤链蛇的Sox基因,并对扩增产物进行了克隆和测序,结果在雌雄个体中共筛选出三个Sox基因,其中有一个为雌雄共有,显示出性别差异性;三个Sox基因编码的氨基酸序列与人相应SOX3,SOX4,SOX22基因的相似性分别为96%,98%,96%。显示出Sox基因在进化上的高度保守性,本文为赤链蛇的性别决定机制研究提供了分子资料。     

Sox and Zfx genes in giant panda

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Cloning and mapping of platypus SOX2 and SOX14: insights into SOX group B evolution

Group B SOX genes, the closest relatives to the sex-determining gene SRY, are thought to have evolved from a single ancestral SOX B by a series of duplications and translocations. The two SOX B genes SOX2 and SOX14 co-localize to chromosome 3q in humans. SOX2 and SOX14 homologues were cloned and characterized in the platypus, a monotreme mammal distantly related to man. The two genes were found to co-localize to chromosome 1q in this species. Proximity of the two related genes has therefore been conserved for 170 Myr, since humans and platypus diverged. The sequence similarity and conserved synteny of these group B genes provide clues to their origin. A simple model of SOX group B gene evolution is proposed.     

The Sry-related HMG box-containing gene Sox6 is expressed in the adult testis and developing nervous system of the mouse.

We have cloned and sequenced a full-length cDNA for the HMG box-containing, SRY-related gene Sox6 from mouse. The deduced protein sequence of Sox6 has considerable homology with that of the previously determined Sox5 sequence. It seems likely that these genes have diverged more recently than other members of the SOX gene family, although the two genes map to different chromosomes in the mouse. In common with Sox5, Sox6 is highly expressed in the adult mouse testis and the HMG domains of both proteins bind to the sequence 5'-AACAAT-3'. This suggests that the two genes may have overlapping functions in the regulation of gene expression during spermatogenesis in the adult mouse. However, Sox6 may have an additional role in the mouse embryo, where it is specifically expressed in the developing nervous system.     

虎纹蛙四个Sox基因的克隆及序列分析

参照人SRY基因HMG－box保守区的序列,设计一对兼并引物,扩增了虎纹蛙的Sox基因,并对扩增产物进行了克隆和测序。结果在雌雄个体中共筛选出四个不同的Sox基因,其序列与人相应SOX基因的相似性分别为92％、94％、985和98％。本研究为探索虎纹蛙的性别决定机制提供了分子资料。     

The Stem Cell Factor Sox2 Is a Positive Timer of Oligodendrocyte Development in the Postnatal Murine Spinal Cord

Myelination in the central nervous system takes place predominantly during the postnatal development of humans and rodents by myelinating oligodendrocytes (OLs), which are differentiated from oligodendrocyte progenitor cells (OPCs). We recently reported that Sox2 is essential for developmental myelination in the murine brain and spinal cord. It is still controversial regarding the role of Sox2 in oligodendroglial lineage progression in the postnatal murine spinal cord. Analyses of a series of cell- and stage-specific Sox2 mutants reveal that Sox2 plays a biphasic role in regulating oligodendroglial lineage progression in the postnatal murine spinal cord. Sox2 controls the number of OPCs for subsequent differentiation through regulating their proliferation. In addition, Sox2 regulates the timing of OL differentiation and modulates the rate of oligodendrogenesis. Our experimental data prove that Sox2 is an intrinsic positive timer of oligodendroglial lineage progression and suggest that interventions affecting oligodendroglial Sox2 expression may be therapeutic for overcoming OPC differentiation arrest in dysmyelinating and demyelinating disorders.     

Group B sox genes that contribute to specification of the vertebrate brain are expressed in the apical organ and ciliary bands of hemichordate larvae

We have identified and characterized the sequence and expression of two Group B Sox genes in the acorn worm, Ptychodera flava. One sequence represents a Group B1 Sox gene and is designated Pf-SoxB1; the other is a Group B2 Sox gene and is designated Pf-SoxB2. Both genes encode polypeptides with an HMG domain in the N-terminal half. Whole-mount in situ hybridization to embryonic and larval stages of P. flava shows that the two genes are expressed in rather similar patterns at these stages. Expression is first detected in the cells of the blastula and subsequently localizes to the ectoderm during gastrulation. As the mouth forms, expression becomes concentrated in the stomodeum region. During morphogenesis of the tornaria larva, expression in the stomodeal ectoderm remains prominent around the mouth and under the oral hood. Later the genes are prominently upregulated in the ciliary bands and the apical organ. These results provide additional evidence that genes playing essential roles in the formation of the chordate dorsal central nervous system function in the development of the ciliary bands and apical organ, neural structures of this non-chordate deuterostome larva.     

扬子鳄4个Sox基因保守区的克隆及序列分析

参考人SRY基因HMG－box的保守区序列,设计一对简并引物,用PCR扩增了扬子鳄Sox基因的HMG－box,并对PCR产物进行了亚克隆和测序。结果在雌雄个体中均筛选到4个不同的Sox基因,无性别差异。其序列与人相应的SOX基因保守区编码序列的相似性分别为91％、96％、100％、96％,分别命名为AS－Sox1,ASSox2,ASSox11,ASSox22。与其他动物相关的Sox/SOX基因的聚类分析结果表明,扬子鳄Sox基因编码的氨基酸序列与进化位置各异的其他动物的Sox/SOX基因编码的氨基酸序列存在高度的同源性,显示出Sox基因在系统进化上的高度保守性。     

Mice null for sox18 are viable and display a mild coat defect

We have previously shown that Sox18 is expressed in developing vascular endothelium and hair follicles during mouse embryogenesis and that point mutations in Sox18 are the underlying cause of cardiovascular and hair follicle defects in ragged (Ra) mice. Here we describe the analysis of Sox18(-/-) mice produced by gene targeting. Despite the profound defects seen in Ra mice, Sox18(-/-) mice have no obvious cardiovascular defects and only a mild coat defect with a reduced proportion of zigzag hairs. A reduction in the amount of pheomelanin pigmentation in hair shafts was also observed; later-forming hair follicles showed a reduced subapical pheomelanin band, giving Sox18(-/-) mice a slightly darker appearance than Sox18(+/+) and Sox18(+/-) siblings. Sox18(-/-) mice are viable and fertile and show no difference in the ability to thrive relative to littermates. Because of the mild effect of the mutation on the phenotype of Sox18(-/-) mice, we conclude that the semidominant nature of the Ra mutations is due to a trans-dominant negative effect mediated by the mutant SOX18 proteins rather than haploinsufficiency as has been observed for other SOX genes. Due to the similarity of SOX18 to other subgroup F SOX proteins, SOX7 and -17, and the overlap in expression of these genes, functional redundancy amongst these SOX proteins could also account for the mild phenotype of Sox18(-/-) mice.