Mice with mutations in the mahogany gene Atrn have cerebral spongiform changes

被引:29
作者
Bronson, RT [1 ]
Donahue, LR [1 ]
Samples, R [1 ]
Naggert, JK [1 ]
机构
[1] Jackson Lab, Bar Harbor, ME 04609 USA
关键词
Atrm; mahogany; brain; mouse; spongiform encephalopathy;
D O I
10.1093/jnen/60.7.724
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
A new mutation characterized by mahogany coat color, sprawling gait, tremors, and severe vacuolization of cerebrum, brainstem. granular layer of cerebellum and spinal cord was discovered in a stock of Mus castaneus mice. Tests for allelism using mice homozygous for 2 known mahogany attractin (Atrn(mg)) mutants showed that the new mutation was an allele of Atrn(mg), Northern analysis showed no expression of Atrn in the new mutants. Southern analysis strongly suggested that the new mutation deleted most of the Arm gene, but was not large enough to affect flanking genes including the prion gene, Prnp, located 1.1 cM from Arm on Chromosome 2. Histopathological analysis of brains from each of the 2 known Atrn(mg) mutants showed that they also have severe spongiform changes. This finding was surprising and raises questions about the mechanism by which mahogany controls appetite and metabolic rate, as recently reported.
引用
收藏
页码:724 / 730
页数:7
相关论文
共 17 条
  • [1] THE EFFECT OF THE SHIVERER MUTATION ON MYELIN BASIC-PROTEIN EXPRESSION IN HOMOZYGOUS AND HETEROZYGOUS MOUSE-BRAIN
    BARBARESE, E
    NIELSON, ML
    CARSON, JH
    [J]. JOURNAL OF NEUROCHEMISTRY, 1983, 40 (06) : 1680 - 1686
  • [2] BINNEY HC, 1986, J NEUROPATHOL EXP NE, V45, P108
  • [3] Bronson RT, 2000, PATHOLOGY OF GENETICALLY ENGINEERED MICE, P239
  • [4] BROWN T, 1998, CURRENT PROTOCOLS MO
  • [5] CHLADNY MJ, 2000, HISTOLOGIC, V32, P34
  • [6] Mahogany (mg) stimulates feeding and increases basal metabolic rate independent of its suppression of agouti
    Dinulescu, DM
    Fan, W
    Boston, BA
    McCall, K
    Lamoreux, ML
    Moore, KJ
    Montagno, J
    Cone, RD
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (21) : 12707 - 12712
  • [7] Agouti and agouti-related protein: Analogies and contrasts
    Dinulescu, DM
    Cone, RD
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (10) : 6695 - 6698
  • [8] The mouse mahogany locus encodes a transmembrane form of human attractin
    Gunn, TM
    Miller, KA
    He, L
    Hyman, RV
    Davis, RW
    Azarani, A
    Schlossman, SF
    Duke-Cohan, JS
    Barsh, GS
    [J]. NATURE, 1999, 398 (6723) : 152 - 156
  • [9] A biochemical function for attractin in agouti-induced pigmentation and obesity
    He, L
    Gunn, TM
    Bouley, DM
    Lu, XY
    Watson, SJ
    Schlossman, SF
    Duke-Cohan, JS
    Barsh, GS
    [J]. NATURE GENETICS, 2001, 27 (01) : 40 - 47
  • [10] Epilepsy and obesity in serotonin 5-HT2C receptor mutant mice
    Heisler, LK
    Chu, HM
    Tecott, LH
    [J]. ADVANCES IN SEROTONIN RECEPTOR RESEARCH: MOLECULAR BIOLOGY, SIGNAL TRANSDUCTION, AND THERAPEUTICS, 1998, 861 : 74 - 78