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  • 1
    Publication Date: 2011-11-16
    Description: The dysfunction of multiple neurotransmitter systems is a striking pathophysiological feature of many mental disorders, schizophrenia in particular, but delineating the underlying mechanisms has been challenging. Here we show that manipulation of a single schizophrenia susceptibility gene, dysbindin, is capable of regulating both glutamatergic and dopaminergic functions through two independent mechanisms, consequently leading to two categories of clinically relevant behavioral phenotypes. Dysbindin has been reported to affect glutamatergic and dopaminergic functions as well as a range of clinically relevant behaviors in vertebrates and invertebrates but has been thought to have a mainly neuronal origin. We find that reduced expression of Drosophila dysbindin (Ddysb) in presynaptic neurons significantly suppresses glutamatergic synaptic transmission and that this glutamatergic defect is responsible for impaired memory. However, only the reduced expression of Ddysb in glial cells is the cause of hyperdopaminergic activities that lead to abnormal locomotion and altered mating orientation. This effect is attributable to the altered expression of a dopamine metabolic enzyme, Ebony, in glial cells. Thus, Ddysb regulates glutamatergic transmission through its neuronal function and regulates dopamine metabolism by regulating Ebony expression in glial cells.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2012-10-02
    Description: Haploids and double haploids are important resources for studying recessive traits and have large impacts on crop breeding, but natural haploids are rare in animals. Mammalian haploids are restricted to germline cells and are occasionally found in tumours with massive chromosome loss. Recent success in establishing haploid embryonic stem (ES) cells in medaka fish and mice raised the possibility of using engineered mammalian haploid cells in genetic studies. However, the availability and functional characterization of mammalian haploid ES cells are still limited. Here we show that mouse androgenetic haploid ES (ahES) cell lines can be established by transferring sperm into an enucleated oocyte. The ahES cells maintain haploidy and stable growth over 30 passages, express pluripotent markers, possess the ability to differentiate into all three germ layers in vitro and in vivo, and contribute to germlines of chimaeras when injected into blastocysts. Although epigenetically distinct from sperm cells, the ahES cells can produce viable and fertile progenies after intracytoplasmic injection into mature oocytes. The oocyte-injection procedure can also produce viable transgenic mice from genetically engineered ahES cells. Our findings show the developmental pluripotency of androgenentic haploids and provide a new tool to quickly produce genetic models for recessive traits. They may also shed new light on assisted reproduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Wei -- Shuai, Ling -- Wan, Haifeng -- Dong, Mingzhu -- Wang, Meng -- Sang, Lisi -- Feng, Chunjing -- Luo, Guan-Zheng -- Li, Tianda -- Li, Xin -- Wang, Libin -- Zheng, Qin-Yuan -- Sheng, Chao -- Wu, Hua-Jun -- Liu, Zhonghua -- Liu, Lei -- Wang, Liu -- Wang, Xiu-Jie -- Zhao, Xiao-Yang -- Zhou, Qi -- England -- Nature. 2012 Oct 18;490(7420):407-11. doi: 10.1038/nature11435. Epub 2012 Sep 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23023130" target="_blank"〉PubMed〈/a〉
    Keywords: Androgens/*metabolism ; Animals ; Biomarkers/metabolism ; Blastocyst/cytology ; Cell Line ; Cell Nucleus ; Chimera/embryology/genetics ; Embryonic Stem Cells/cytology/*physiology ; Epigenesis, Genetic ; Female ; *Haploidy ; Male ; Mice ; Mice, Transgenic/embryology/genetics/*growth & development ; Models, Animal ; Models, Genetic ; Oocytes/cytology/growth & development/metabolism ; Pluripotent Stem Cells/cytology/physiology ; Sperm Injections, Intracytoplasmic ; Spermatozoa/metabolism/transplantation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
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