Disruption of the centromere protein J gene, CENPJ (CPAP, MCPH6, SCKL4), which is a highly conserved and ubiquitiously expressed centrosomal protein, has been associated with primary microcephaly and the microcephalic primordial dwarfism disorder Seckel syndrome. The mechanism by which disruption of CENPJ causes the proportionate, primordial growth failure that is characteristic of Seckel syndrome is unknown. By generating a hypomorphic allele of Cenpj, we have developed a mouse (Cenpj(tm/tm)) that recapitulates many of the clinical features of Seckel syndrome, including intrauterine dwarfism, microcephaly with memory impairment, ossification defects, and ocular and skeletal abnormalities, thus providing clear confirmation that specific mutations of CENPJ can cause Seckel syndrome. Immunohistochemistry revealed increased levels of DNA damage and apoptosis throughout Cenpj(tm/tm) embryos and adult mice showed an elevated frequency of micronucleus induction, suggesting that Cenpj-deficiency results in genomic instability. Notably, however, genomic instability was not the result of defective ATR-dependent DNA damage signaling, as is the case for the majority of genes associated with Seckel syndrome. Instead, Cenpj(tm/tm) embryonic fibroblasts exhibited irregular centriole and centrosome numbers and mono- and multipolar spindles, and many were near-tetraploid with numerical and structural chromosomal abnormalities when compared to passage-matched wild-type cells. Increased cell death due to mitotic failure during embryonic development is likely to contribute to the proportionate dwarfism that is associated with CENPJ-Seckel syndrome.
Pubmed ID: 23166506 RIS Download
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Detailed multidimensional digital multimodal atlas of C57BL/6J mouse nervous system with data and informatics pipeline that can automatically register, annotate, and visualize large scale neuroanatomical and connectivity data produced in histology, neuronal tract tracing, MR imaging, and genetic labeling. MAP2.0 interoperates with commonly used publicly available databases to bring together brain architecture, gene expression, and imaging information into single, simple interface.Resource to visualise mouse development, identify anatomical structures, determine developmental stage, and investigate gene expression in mouse embryo. eMouseAtlas portal page allows access to EMA Anatomy Atlas of Mouse Development and EMAGE database of gene expression.EMAGE is freely available, curated database of gene expression patterns generated by in situ techniques in developing mouse embryo. EMA, e-Mouse Atlas, is 3-D anatomical atlas of mouse embryo development including histology and includes EMAP ontology of anatomical structure, provides information about shape, gross anatomy and detailed histological structure of mouse, and framework into which information about gene function can be mapped.
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View all literature mentionslaboratory mouse with name C57BL/6NTac from MGI.
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