Biology Reference
In-Depth Information
II. EXAMPLE: SIMULATION OF THE EFFECTS OF SCN
ABLATION AND TRANSPLANTATION ON FREE-RUNNING
LOCOMOTOR ACTIVITY
Like many rodents, golden (or Syrian) hamsters, Mesocricetus auratus, are
nocturnal. Their locomotor activity begins when the lights go out, and
one of the activities they pursue very avidly is wheel-running. It is easy
to obtain data of the hamster's locomotor activity by electronically
monitoring the wheel rotation. In a wild-type hamster, exposure to a
light/dark (LD) cycle of 14 hours of light and 10 hours of dark (LD 14:10)
will entrain the hamster and result in wheel-running activity at about the
same time every day, even when the hamster is switched to dark/dark
(DD) conditions. The results obtained under these constant conditions
are called free-running because there is no signal (zeitgeber) to reset
the hamster's biological clock. Measuring the wheel-running activity
of a wild-type golden hamster in DD conditions is known to yield a
free-running period of about 24.1 hours.
In 1988, Martin Ralph and Michael Menaker reported on a period
mutation in the golden hamster (Ralph and Menaker [1988]). The first
mutant hamster, a male, was recognized because it had a free-running
period of 22.0 hours. Ralph and Menaker bred the mutant male with
several normal females, and then subjected the F
1
animals to
entrainment (LD 14:10) followed by constant dark to see how they
behaved. Half of the F
1
animals had a free-running period averaging 22.3
hours. They were designated with the abbreviation T
s
(for short tau or
period). The other half had a period close to 24 hours. They were
designated as T
n
. When T
s
animals were interbred, three types of
offspring were produced: T
n
with a period of 24 hours, T
s
with a period of
22 hours, and a new super-short phenotype, T
ss,
with a period of
approximately 20 hours. These results are consistent with a mutation in a
single gene, called tau, that is acting in a semidominant fashion (see
Chapter 3). The normal hamster has two copies of the wild-type gene;
the T
s
hamster (with the 22-hour period) is a heterozygote with one
normal and one mutant copy of tau; and the super-short mutant has
two mutant copies. We shall refer to the homozygous super-short hamster
as tau
ss
.
The identity of the protein expressed by the tau gene is now known to be
casein kinase I epsilon (CKI
). A kinase is an enzyme that places
phosphate groups on proteins, in this case the mammalian proteins
PER1 and PER2. It is similar in this way to the Drosophila gene double
time (see Figure 11-6). Phosphorylation of a protein may alter its activity
(increasing or decreasing it) or its cellular location or may mark it for
destruction. In any event, the addition of such a large charged group is
likely to be significant, and so it is not surprising that a change in the
activity of CKI
e
e
because of mutation would have a radical effect on the
period length.
