[Press Release] First Circadian Clock Gene Identified and Cloned in Mammals

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Title : First Circadian Clock Gene Identified and Cloned in Mammals
Type : Press Release
NSF Org: OD / LPA
Date : May 15, 1997
File : pr9735

Embargoed until 5 P.M., EDT
Media contact: May 15, 1997
Cheryl Dybas NSF PR 97-35
(703) 306-1070/cdy...@nsf.gov

Program contact:
Chris Platt
(703) 306-1424/cpl...@nsf.gov

FIRST CIRCADIAN CLOCK GENE
IDENTIFIED AND CLONED IN MAMMALS

Scientists affiliated with the National Science Foundation's
(NSF) Center for Biological Timing have identified and cloned a
gene for the biological clock in a mouse, the first such gene to
be identified at the molecular level in a mammal.

The identification of the "Clock" gene was proven by
restoring a functioning biological clock in a line of mutant mice
which had lost normal circadian rhythms. The researchers
accomplished this by inserting DNA for the gene into developing
embryos, which not only grew to have normal biological clocks,
but incorporated them into their own genetic material, passing
them on to their descendants.

"The identification of the `Clock' gene is definitive," said
Joseph Takahashi, professor of neurobiology and physiology at
Northwestern University in Evanston, Illinois, and author of two
articles appearing in the Friday, May 16, 1997 issue of the
journal Cell.

"This is the first time that the discovery of a mammalian
gene regulating behavior has been accompanied by simultaneous
proof that the gene has been located, by `rescuing' the lost
function of the gene," Takahashi said.

The work is the result of the Clock Genome Project at the
NSF Center for Biological Timing. The project uses "forward
genetics" to discover the genes regulating circadian clocks in
mice, fruit flies, and plants.

"The cloning and characterization of the Clock gene in mice
is an important step forward in our understanding of the
mechanisms underlying biological clocks in mammals. The work
should ultimately lead to insights into the regulation of human
circadian behaviors, such as the rhythms in sleep and
wakefulness," Gene Block, director of the NSF center said.

All life forms, including humans, possess internal 24-hour
clocks, known as "circadian" (from the Latin "circa," about, and
"dian", a day) clocks, which regulate our daily activities such
as sleep and waking. Difficulties in readjusting our clocks
cause jet lag and shift work problems, as well as some types of
sleep disorders. The circadian clock impacts almost every level
of our bodily functions. A new understanding of the nature of
the Clock gene may make it possible to target it with drugs that
would help restore normal clock functioning.

"This research provides direct evidence that clocks in
mammals may be built with the same principles as those seen in
fruit flies and fungi," Takahashi said. Fruit flies and fungi
were until now the only organisms in which clock genes had been
cloned and identified at the molecular level.

Takahashi's approach used a novel strategy called "rescue"
to help locate the Clock gene. The behavior of the mice was
used to track down the responsible gene. The team inserted a
number of different artificial chromosomes carrying normal DNA
into the embryos of mutant mice, to see which might have an
impact on the mouse's behavior. One of these proved to be able
to restore the biological clock function in the mutated mice.
This finding helped the team zero in on the precise location of
the gene.

Evidence of the Clock gene was found to be very high in two
tissues known to be able to generate circadian signals, the eye
and the suprachiasmatic nucleus (SCN) of the hypothalamus.
Surprisingly, Clock was also found in other areas of the brain as
well as the testis, ovary, liver, heart, lung and kidney.
According to Takahashi, "This widespread expression of Clock
leads to the speculation that Clock may regulate timing at many
different levels in cells and tissues in the entire body."

-NSF-

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