M.S., Cell Biology, Univ. Cincinnati, USA
Ph.D., Molecular, Cellular and Developmental Biology, Iowa State Univ., USA
Post-Doc Microbiology, School of Medicine, East Carolina University 1981-1982
Greenville, NC, USA
王穎之
許家宜
陳煒溶
楊玉綉
林惠竹
簡朝烽
張南驥
吳信志
李坤雄
周元華
林慶波
梁庚辰
陳景宗
蘇東平
1. Revelation of Neural Gene Functions using Transgenic and Knockout Mice Approach
Functional characterization of novel neural genes and those previously uncovered in CNS areas implicated in cognition are currently underinvestigation both in vitro and in vivo. The candidate genes are 2 adrenoceptor subtype genes Adra2b and Adra2c encoding a2B and a2C adrenoceptor respectively. a2 adrenoceptor subtypes mediate the specific effect of norepinephrine via G protein-coupled signal transduction pathways in selected areas in CNS. Luzp is the gene encoding a putative transcription factor LUZP predominantly expressed in brain areas such as temporal cortex, hippocampus and cerebellum.
Promoter-reporter transgenic mouse lines of both a2B and a2C adrenoceptor have been established in which cis-elements-reporter constructs linking lacZ were used to trace the temporal and spatial expression of specific receptor subtypes as directed by different domains of regulatory region of its gene. These models were employed to facilitate the study of receptor expression regulation.
We have also established 3 lines of knock-out mouse models in which the candidate genes; Adra2b, Adra2c and Luzp, were each targeted disrupted and a reporter gene lacZ was in-frame inserted downstream to the regulatory region of respective genes. The adrenoceptor subtype deficient mutants provide in vivo models in which their respective expression atlas in brain may be established and their functional significance in emotion regulation (e.g., aggression and addictive behaviors) may be explored. The LUZP-null mice are currently employed to delineate its role in neural tube closure in embryonic brain. The selective expression of LUZP in hippocampus prompted the use of heterozygous Luzp-mutant to delineate its role in stress response by pharmacogenetic approach. Condition knockout mouse lines will be established employing the Tet-on system and specific promoter driven Cre-loxP recombinase system. The mutant mice with definitive molecular lesion are excellent in vivo models in which the functional involvement of each candidate gene at the cellular, system, behavioral and cognitive levels may be assessed.
2. Immortalization and Characterization of Neural Cell Lines
The myelin deficient (msd) rat is a model system for human demyelinating diseases. The mutant is characterized by defective oligodendrocytes, the central myelin synthesizing glia. We have established and characterized a clonal oligodendrocyte line CBII. Further characterization in terms of its functional competence; the capacity to make myelin both in vitro and in vivo systems are under pursue. In addition, we have established a murine neuronal cell line DM, derived from embryonic (E13) mesencephalon and used it as an in vitro model system for mesolimbic dopaminergic neurons. We are in the process of characterizing its apoptotic response to addictive drugs such that neural protective strategies may be devised.
Human Brain Project: from Genes to Cognitiion: Unvaveling Neural Genes in Brain Areas Implicated in Cognition
Structure and Function of YM-1, a Transiently Expressed Protein Synthesized by Activated Murine Macrophages: Temporal and Spatial Expression of Ym1 im Mice: Neuroimmunological Corelates
Establishment of Transgenic Mice in Which the Expression of Cre Recombinase is Brain Region Specific and Under Temporal Control
The Functional Significance of Luzp During Development
Exploring the Modulatory Role of Norepinephrine in Emotion and Memory Using Ada2c-KO/lacZ-KI Mutnat Mice
Chien A, DB Edgar and JM Trela (1976) DNA polymerase from the extreme thermophile Thermus aquaticus. J Bact. 127(3): 1550-1557. First to Discover and Report the Purification and Characterization of DNA polymerase of Thermus aquaticus (Taq polymerase)-- Taq polymerase is Key to the Sucessful Application of Polymerase Chain Reaction (PCR)
Chang AC and HD Dellmann (1981) Biosynthesis and axoplasmic transport of neurophysins in the hypothalamo-neurohypophsyial system of the grass frog Rana pipiens. in ”Neurosecretion: Molecules, Cells, System” DF Farner & K Lederis (eds), Plenum Press, New York, pp. 473-474.
Chang AC and HD Dellmann. (1981) Light and electron microscopic observations in the hypothalamo- neurohypophysial system of the grass frog Rana pipiens after microiontophoresis of vinblastine into the median eminence. in “Neurosecretion: Molecules, Cell, Systems” DF Farner & K Lederis (eds), Plenum Press, New York, pp. 471-472.
Chang AC and HD Dellmann. (1984) A fine structure study of the formation of temporary swellings (Herring bodies) and reversible degeneration of neurosecretory axons following microiontophoretic ejection of vinblastine into the hypothalamo-neurohypophysial tract of the frog Rana pipiens. Exp Brain Res 53: 357-369.
Chang AC and HD Dellmann. (1984) Biosynthesis and axoplasmic transport of neurophysins in the hypothalamo-neurohypophysial system of Rana pipiens. J Neurosci 4(7): 1840-1849.
Chang AC, CJ Alyea, LC Triarhou, WC Low and B Ghetti. (1988) Expression of the developmentally regulated polypeptide PEP-19 by Purkinje cells transplanted to the cerebellum of pcd mutant mice. Anat Rec 220(4): 20-21
Chang AC, LC Triarhou, CJ Alyea, WC Low and B Ghetti. (1988) Reactive gliosis in the cerebellum of pcd mutant host does not prevent the survival and differentiation of transplanted Purkinje cells. J Neuropathol Exp Neurol 47(3): 384
Chang AC, LC Triarhou, CJ Alyea, WC Low and B Ghetti. (1989) Developmental expression of polypeptide PEP-19 in cerebellar cell suspensions transplanted into the cerebellum of pcd mutant mice. Exp Brain Res 76(3): 639-645
Ghetti B, LC Triarhou, CJ Alyea, WC Low and AC Chang. (1990) Timing of neuronal replacement in cerebellar degenerative ataxia of Purkinje cell type. Prog Brain Res 82: 197-202
Chang AC, TF Ho and NC Chang. (1990) In vitro amplification by polymerase chain reaction of a partial gene encoding the third subtype of a2 adrenergic receptor in human. Biochem Biophys Res Commun 172(2): 817-823.
Chang AC, YH Lin, RL chou, GY Liao and NC Chang, (1992) Characterization of a glial associated antigen GA-1 by monoclonal antibody. Neurosci Lett 140: 192-196.
Chen WM, AC Chang, BJ Shie, YH Chang and NC Chang. (1992) Molecular cloning and characterization of a mouse 汹a2C2 adrenoceptor subtype gene. Biochim Biophys Acta 1171: 219-223
Sun SH and AC Chang. (1992) Effects of sodium butyrate on phospholipid metabolism in a clonal rat brain oligodendrocyte cell line CB-II. J Chin Biochem 21(2): 51-60.
Chang YH, NC Chang, WM Chen and AC Chang. (1993) Molecular characterization of a murine homologue of a2C4 adrenoceptor subtype gene. Biochem Mol Biol Internatl 29(3): 467-474
Chang AC and B Ghetti. (1993) Embryonic cerebellar graft development during acute phase of gliosis in the cerebellum of pcd mutant mice. Chinese J Physiol 36(3): 141-149
Chang NC, Jenkins NA, Gilbert DJ, Copeland NG, Chang YH, Chen, WM and Chang AC. (1994) Assignment of two a2 adrenoceptor subtype genes to murine chromosomes. Neuroscience Lett 167: 105-108
Wu SC, Chang NC, Chang AC, Chen WK, Yang TS, Shem PC and Lee KH. (1995) Establishment of the technique of mouse embryo pronucleus microinjection. J Chinese Soc Animal Sci 24(2): 181-189
Chen WM, AC Chang, CM Wang, CC Lin and NC Chang. (1996) Characterization of the regulatory region of murine a2C2 gene. Neurosci Lett 210: 33-36
Sun DS, AC Chang, NA Jenkins, DJGilbert, NG Copeland and NC Chang. (1996) Identification, molecular characterization and chromosomal localization of the cDNA encoding a novel leucine zipper motif-containing protein. Genomics 36: 54-62.
Fan SS, Chang NC, Chang AC and Yin HS. (1997) Differential expression of the GABAA receptor 汹subunit in developing brain. NeuroReport 8: 2399-2404
Chang NC, Hung SI, Hwa KY, Kato I, Chen JE, Liu CH and Chang AC. (2001) A macrophage protein Ym1 transiently expressed during inflammation is a novel mammalian lectin. J Biol Chem 276: 17497-17506
Sun YJ, Chang, NC, Hung SI, Chang AC, Chou CC and Hsiao CD. The crystal structure of a novel mammalian lectin, Ym1 suggests a saccharide binding site. J. Biol Chem 276: 17507-17514 (2001)
Lee MWY, Chang AC, Sun DS, Hsu CY and Chang NC. Restricted expression of LUZP in neural lineage cells: a study in embryonic stem cells. J Biomed Sci. 8: 504-511 (2001)
Hung SI, Chang AC, Kato I and Chang NC. Transient expression of Ym1, a heapin-binding lectin, during developmental hematopoiesis and inflammation. J Leukoc Biol 72(1): 72-82 (2002)
Wang GS, Chang NC, Wu SC and Chang AC. Regulated expression of a2B adrenoceptor during development. Dev Dynamics 225:142-152 (2002)
Chen WK, Chang NC, Chang YH, Chang, KC, Wu SC, Yang TS, Wu SM and Chang AC. Characterization of the regulatory region of Adra2c, the gene encoding the murine a2C adrencoeptor subtype. J Biomed Sci. 11: 886-901 (2004)
