Reduced sleep in Drosophila shaker mutants

被引:331
作者
Cirelli, C
Bushey, D
Hill, S
Huber, R
Kreber, R
Ganetzky, B
Tononi, G
机构
[1] Univ Wisconsin, Dept Psychiat, Madison, WI 53719 USA
[2] Univ Wisconsin, Genet Lab, Madison, WI 53706 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nature03486
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Most of us sleep 7-8 h per night, and if we are deprived of sleep our performance suffers greatly; however, a few do well with just 3-4 h of sleep-a trait that seems to run in families. Determining which genes underlie this phenotype could shed light on the mechanisms and functions of sleep. To do so, we performed mutagenesis in Drosophila melanogaster, because flies also sleep for many hours and, when sleep deprived, show sleep rebound and performance impairments. By screening 9,000 mutant lines, we found minisleep (mns), a line that sleeps for one-third of the wild-type amount. We show that mns flies perform normally in a number of tasks, have preserved sleep homeostasis, but are not impaired by sleep deprivation. We then show that mns flies carry a point mutation in a conserved domain of the Shaker gene. Moreover, after crossing out genetic modifiers accumulated over many generations, other Shaker alleles also become short sleepers and fail to complement the mns phenotype. Finally, we show that short-sleeping Shaker flies have a reduced lifespan. Shaker, which encodes a voltage-dependent potassium channel controlling membrane repolarization and transmitter release, may thus regulate sleep need or efficiency.
引用
收藏
页码:1087 / 1092
页数:6
相关论文
共 50 条
[1]   RESTORATION OF CIRCADIAN BEHAVIORAL RHYTHMS BY GENE-TRANSFER IN DROSOPHILA [J].
BARGIELLO, TA ;
JACKSON, FR ;
YOUNG, MW .
NATURE, 1984, 312 (5996) :752-754
[2]   APAMIN, A SELECTIVE SK POTASSIUM CHANNEL BLOCKER, SUPPRESSES REM-SLEEP WITHOUT A COMPENSATORY REBOUND [J].
BENINGTON, JH ;
WOUDENBERG, MC ;
HELLER, HC .
BRAIN RESEARCH, 1995, 692 (1-2) :86-92
[3]   Sleep homeostasis and models of sleep regulation [J].
Borbély, AA ;
Achermann, P .
JOURNAL OF BIOLOGICAL RHYTHMS, 1999, 14 (06) :557-568
[4]   Extensive and divergent effects of sleep and wakefulness on brain gene expression [J].
Cirelli, C ;
Gutierrez, CM ;
Tononi, G .
NEURON, 2004, 41 (01) :35-43
[5]   Searching for sleep mutants of Drosophila melanogaster [J].
Cirelli, C .
BIOESSAYS, 2003, 25 (10) :940-949
[6]   Molecular architecture of the KvAP voltage-dependent K+ channel in a lipid bilayer [J].
Cuello, LG ;
Cortes, DM ;
Perozo, E .
SCIENCE, 2004, 306 (5695) :491-495
[7]   Functional Genomics of Sleep and Circadian Rhythm -: Invited review:: Integration of human sleep-wake regulation and circadian rhythmicity [J].
Dijk, DJ ;
Lockley, SW .
JOURNAL OF APPLIED PHYSIOLOGY, 2002, 92 (02) :852-862
[8]   The suprachiasmatic nucleus regulates sleep timing and amount in mice [J].
Easton, A ;
Meerlo, P ;
Bergmann, B ;
Turek, FW .
SLEEP, 2004, 27 (07) :1307-1318
[9]   Increased motor drive and sleep loss in mice lacking Kv3-type potassium channels [J].
Espinosa, F ;
Marks, G ;
Heintz, N ;
Joho, RH .
GENES BRAIN AND BEHAVIOR, 2004, 3 (02) :90-100
[10]   EVIDENCE FOR GENETIC INFLUENCES ON SLEEP DISTURBANCE AND SLEEP PATTERN IN TWINS [J].
HEATH, AC ;
KENDLER, KS ;
EAVES, LJ ;
MARTIN, NG .
SLEEP, 1990, 13 (04) :318-335