THE APOLIPOPROTEIN(A) GENE IS REGULATED BY SEX-HORMONES AND ACUTE-PHASE INDUCERS IN YAC TRANSGENIC MICE

被引:106
作者
FRAZER, KA [1 ]
NARLA, G [1 ]
ZHANG, JL [1 ]
RUBIN, EM [1 ]
机构
[1] GRAD THEOL UNION,LAWRENCE BERKELEY LAB,CTR HUMAN GENOME,BERKELEY,CA 94720
关键词
D O I
10.1038/ng0495-424
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
High plasma concentrations of apolipoprotein (a) (apo(a)) have been implicated as a major independent risk factor for atherosclerosis in humans. Apo(a) is a large, evolutionarily new gene (present primarily in primates) for which considerable controversy exists concerning the factors that regulate its expression. To investigate the in vivo regulation of apo(a), we have created several lines of YAC transgenic mice containing a 110-kb human apo(a) gene surrounded by greater than 60 kb of 5' and 3' flanking DNA. Studies in humans have suggested that acute-phase inducers increase and sex steroids decrease apo(a) concentrations, but these results are controversial. Analysis of the YAC transgenic mice conclusively supports the hypothesized role of sex steroids and refutes the suggested role of acute-phase inducers in regulating the apo(a) gene.
引用
收藏
页码:424 / 431
页数:8
相关论文
共 33 条
  • [1] GENETICS OF THE QUANTITATIVE LP(A) LIPOPROTEIN TRAIT .3. CONTRIBUTION OF LP(A) GLYCOPROTEIN PHENOTYPES TO NORMAL LIPID VARIATION
    BOERWINKLE, E
    MENZEL, HJ
    KRAFT, HG
    UTERMANN, G
    [J]. HUMAN GENETICS, 1989, 82 (01) : 73 - 78
  • [2] APOLIPOPROTEIN(A) GENE ACCOUNTS FOR GREATER THAN 90-PERCENT OF THE VARIATION IN PLASMA LIPOPROTEIN(A) CONCENTRATIONS
    BOERWINKLE, E
    LEFFERT, CC
    LIN, JP
    LACKNER, C
    CHIESA, G
    HOBBS, HH
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (01) : 52 - 60
  • [3] CLONING OF LARGE SEGMENTS OF EXOGENOUS DNA INTO YEAST BY MEANS OF ARTIFICIAL CHROMOSOME VECTORS
    BURKE, DT
    CARLE, GF
    OLSON, MV
    [J]. SCIENCE, 1987, 236 (4803) : 806 - 812
  • [4] THE HUMAN APOLIPOPROTEIN(A) PLASMINOGEN GENE-CLUSTER CONTAINS A NOVEL HOMOLOG TRANSCRIBED IN LIVER
    BYRNE, CD
    SCHWARTZ, K
    MEER, K
    CHENG, JF
    LAWN, RM
    [J]. ARTERIOSCLEROSIS AND THROMBOSIS, 1994, 14 (04): : 534 - 541
  • [5] CALLOW MJ, 1994, P NATL ACAD SCI USA, V92, P21130
  • [6] CHLESA G, 1992, J BIOL CHEM, V287, P24369
  • [7] SEQUENCE POLYMORPHISMS IN THE APOLIPOPROTEIN(A) GENE - EVIDENCE FOR DISSOCIATION BETWEEN APOLIPOPROTEIN(A) SIZE AND PLASMA LIPOPROTEIN(A) LEVELS
    COHEN, JC
    CHIESA, G
    HOBBS, HH
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1993, 91 (04) : 1630 - 1636
  • [8] PROLIFERATION OF HUMAN SMOOTH-MUSCLE CELLS PROMOTED BY LIPOPROTEIN(A)
    GRAINGER, DJ
    KIRSCHENLOHR, HL
    METCALFE, JC
    WEISSBERG, PL
    WADE, DP
    LAWN, RM
    [J]. SCIENCE, 1993, 260 (5114) : 1655 - 1658
  • [9] LACK OF ASSOCIATION BETWEEN SEX-HORMONES AND LP(A) CONCENTRATIONS IN AMERICAN AND FINNISH MEN
    HAFFNER, SM
    MYKKANEN, L
    GRUBER, KK
    RAINWATER, DL
    LAAKSO, M
    [J]. ARTERIOSCLEROSIS AND THROMBOSIS, 1994, 14 (01): : 19 - 24
  • [10] HENRIKSSON P, 1992, J CLIN INVEST, V89