/ . Embryo!. exp. Morph. Vol. 33, 4, pp. 831-844, 1975
Printed in Great Britain
831
The growth of rats and mice vibrissae under
normal and some abnormal conditions
ByLAMEES IBRAHIM1 AND E.A.WRIGHT 1
From the Department of Morbid Anatomy,
King's College Hospital Medical School, London
SUMMARY
The growth of hair from the mystacial vibrissal follicles of C3H mice and Wistar rats has
been measured for up to seven cycles. Normally growth in length and thickness was regular
and little affected by age or sex. Plucking vibrissae at any stage during the growing period
was followed by the appearance of a new vibrissa 8-11 days later. Plucking when growth had
ceased had no effect on the time of appearance of the subsequent cycle. New whiskers
emerging after plucking grew at the normal rate. Withholding food slowed the growth of
vibrissae within 1 day. Normal growth was re-established 3 days after return to full diet.
INTRODUCTION
The growth of skin is difficult to observe directly in vivo because it is not easy
to measure either the contribution by the basal cells on the one hand or the loss
of cells from the surface on the other. Also, the skin thickness varies and is
difficult to assess in vivo. The hair follicle is a specialized form of skin where
the growth of the epidermal element can be accurately followed. Any decrease in
epidermal cell production will reduce the amount of hair being produced.
Most previous investigations of hair growth have been made on relatively
large populations of hairs. Measurement of individual hairs is difficult owing to
their small size. However, the vibrissae of mice and rats are relatively large and
can be accurately measured by simple instruments. In addition, the vibrissae are
found as a constant pattern of follicles (Danforth, 1925) which are bilaterally
symmetrical. It is therefore possible to follow a single vibrissal follicle and its
vibrissa throughout its life-history. If it is subjected to local interference the
vibrissa on the opposite side is an excellent control.
In the present paper we have examined normal hair growth in relation to a
variety of local and general factors by observing the length and width of individual hairs.
A preliminary account of some of the results on mice has already been published (Wright, 1965).
1
Authors' address: Department of Morbid Anatomy, King's College Hospital Medical
School, Denmark Hill, London, S.E. 5, U.K.
832
L. IBRAHIM AND E. A. WRIGHT
MATERIALS AND METHODS
Animals
Male and female inbred C3H mice, closed-colony white mice, and closedcolony Wistar-derived albino rats bred at King's College Hospital Medical
School were used.
Measurements
Vibrissae were measured using the same method as described previously
(Wright, 1964). Vibrissae under observation were usually measured once or
twice weekly, but more frequently for some experiments. Because the tip was
difficult to see they were cut near the skin surface just before the first measurement and thereafter whenever the hairs grew to 10-15 mm length. All cut
portions were mounted on glass slides. The measurements of length of the remaining portion of the hair were made using a graduated capillary glass tube
which was approximately 0-5 mm outside diameter and 0-3 mm internal diameter for mice and 0-6 and 0-4 mm respectively for rats. These tubes fitted
neatly over the hair stump and could be pressed gently against the skin surface.
An accuracy of 0-1 mm could easily be obtained by using a binocular microscope (x 16) and could be regularly repeated by the same or different observers.
If the whole hair was required the hair shaft with its 'club' could be plucked
shortly after growth had ceased. This did not interfere with the growth of the
next hair.
The width was measured from mounted hairs. Mouse and rat vibrissae are
almost round in cross section.
RESULTS AND OBSERVATIONS
1. Arrangement ofmystacial vibrissae
Rats and mice have well-defined antero-posterior rows and dorso-ventral
columns of vibrissae which are identical on both sides of the face. Each whisker
follicle position has been named by Danforth (1925) and we have used this
nomenclature throughout (Fig. 1).
2. Normal growth of vibrissae
All the vibrissae follow the shape of growth curve shown in Fig. 2. In mice,
E, F, G and H whiskers grow 1 mm a day for about 4 weeks then slow down for
a few days before stopping. The new whisker appears approximately 1 week
after the previous whisker stops increasing in length. The old whisker usually
falls out when the new whisker is about ^-f of its full length. In rats, E, F, G
and H grow 1-5 mm a day for about 4 weeks, slow down for approximately
1 week, then stop. They usually fall out 3 weeks later.
Cutting any part of the vibrissa above the skin does not affect the rate of
growth. Thus the growth curves, which usually included several cuttings, are
833
Growth of rats and mice vibrissae
f
16
E %
27
10
t
t
23
18
11
24
t
%
17
12
G|
27
t
23
t
16
12
H |
27
t
21
#
14
12
t
7
II
F •
29
i
6
III
8
t
t
9
IV
4
t
t
•
Fig. 1. Arrangement of mystacial vibrissal follicles on the right side of the mouse.
The letters and roman numbers represent the names of the follicles. The number
below each dot is a representative length of vibrissae produced by this follicle.
30
20
10
100
200
Days
Fig. 2. Six complete cycles and part of the seventh of an F vibrissa of a male C3H
mouse starting shortly after birth.
linear, and when one side was cut and the other left uncut the usual symmetry
was observed.
The E vibrissa on the right side of an adult female C3H mouse was measured
over short periods on 2 successive days. The growth curve was almost linear
(Fig. 3).
As long as the follicle and its mirror image on the other side is not interfered
with, their length, growth rate and other characteristics remain remarkably
similar for long periods. For example, the F vibrissae on each side were followed
for seven cycles over a period of 8 months and were found to be out of step by
only 2 mm or 2 days. This small asynchrony represents a 'loss' of time of less
than 1 % - a precision rarely met in a biological 'clock'.
834
L.IBRAHIM AND E. A. WRIGHT
4
r
.60
I
I
I
I
12
I
I
I
16
20
Time (h)
I
I
24
I
I
I
28
I
32
Fig. 3. The growth of an E vibrissa of an adult female C3H mouse measured four
times at 2 h intervals on the first day and three times at 4 h intervals on the next
day. The points represent the mean of ten measurements each and the bars are the
extreme ranges.
Table 1. The range of lengths and average rate of growth of the five posterior
dorso-ventral rows of vibrissae in a young adult male mouse and a young adult
male rat
Mice
Rats
A
Vibrissae
Length
(mm)
Rate of
growth
(mm/day)
Length
(mm)
Rate of
growth
(mm/day)
E, F, G, H
Ia-Va
Ib-Vb
Ic-Vc
Id-Vd
27-30
21-24
16-18
10-12
7-9
10
0-8
0-6
0-3
0-3
45-60
40-44
33-35
23-25
11-16
1-5
1-3
1-1
0-9
0-6
Vibrissae in the same dorso-ventral column are approximately the same
length. They decrease in length postero-anteriorly. The posterior column of
follicles contains the largest vibrissae and was therefore most frequently used.
The F whisker in mice may be 2 mm longer than the E, G and H vibrissae. In
the rat the E and F vibrissae are usually slightly smaller than the G and H
vibrissae.
In some rats the G vibrissal follicle produced two small vibrissae which were
about 30-35 mm in length instead of a large one which was normally between
55-60 mm in length. This deviation was observed in the first three cycles before
the animal was killed. This phenomenon was seen in approximately 25 % of
835
Growth of rats and mice vibrissae
A
50
-la
-Ib
-Ic
Id
40-
to
%
20-
10-
20
50
100
T
150
200
Age (days)
40-
30-
20-
10-
20
50
100
Age (days)
150
200
Fig. 4. Five to eight growth cycles of the rat's vibrissae la, Ib, Ic and Id.
Fig. 4A, male; B, female, g, The whisker was plucked accidentally, f, A cycle of
d whisker could not be recorded because of a technical fault in the second measurement, k, A late short cycle of b whisker; since the next cycle was in the correct
place and growing at a normal rate, the damage to the follicle was presumably
temporary, e, Tip of the vibrissa was broken off when first observed.
the rats observed. Although no systematic observations were made, the appearance in all members of some litters suggests a genetic basis.
Length and rate of growth of the five posterior columns were measured and
recorded (see Table 1). Fig. 4 A and B shows 5-8 cycles of vibrissae in the rat
for follicles Ia-d.
3. Width of vibrissae
The diameters of vibrissae increase approximately linearly with the length.
In mice E, F, G and H vibrissae are 2-5 jum at their tips and 70-90 fim at their
widest part excluding the club. In rats E, F, G and H vibrissae are 3-5 /im at
their tips and 160-180/tm at the widest part excluding the club. In both cases
the increase in width occurs steadily from the tip to the base. The width of
52
EMB 33
836
L. IBRAHIM AND E. A. WRIGHT
Vb
Va
30
10
20
Distance from tip (mm)
Fig. 5. Width measurements of F, Ya, Vb, Vc and Vd vibrissae from the right
side of an adult male C3H mouse. The next generation of F is plotted to show
the consistency in width of the vibrissae produced from the same follicle. O,
Mature F; A, next generation of F; • , Va; V, Vb; O, Vc; + , Vd.
180 —
140-
Ic
Id
70-
10
20
30
40
Distance from tip (nun)
50
Fig. 6. Width measurements of F, la, Ib, Ic and Id vibrissae of an adult male rat.
successive generations from the same follicle closely follows the same pattern
(Figs. 5, 6).
The second generation of mouse vibrissae are the same length and width as
the first generation (Figs. 2, 5).
The widths and lengths of a, b, c and d vibrissae in mice and rats are shown
in Figs. 5 and 6 (F vibrissa is included for comparison).
837
Growth of rats and mice vibrissae
Table 2. Average growth rates and final lengths of E, F, G and H vibrissae in
five female C3H mice of different ages in the penultimate and ultimate cycles
before death
(Numbers of vibrissae measured are in parentheses.)
Ultimate cycle
Penultimate cycle
A
Age at
death
(months)
i
Growth rate
(mm/day)
9*
—
15t
0-99 (4)
0-87 (4)
0-88 (4)
21$
28$
32|
—
t
•>
Final length
(mm)
—
25-1 (4)
27-2 (3)
27-3 (3)
25-0 (1)
Growth rate
(mm/day)
Final length
(mm)
094 (4)
0-69 (3)
0-82 (4)
0-80 (4)
0-82 (3)
27-5 (4)
—
25-6 (4)
22-8 (3)
—
* Accidentally killed.
t Died of natural causes before completion of last cycle.
% Died of natural cause.
30-i
20-
0J
0
10
20
30
40
50
60
70
80
Fig. 7. Chart of the length of E, F, G and H vibrissae on the right side of a C3H
female mouse 25 months of age at the commencement of the observation. The
growth rates in mm/day were measured on the straight parts of the growth curve
and are recorded on each slope, (a) A small portion of the tip of the vibrissa had
been broken off when first observed.
4. The effect of some factors on whisker growth
(i) Age
Male and female C3H mice and Wistar-derived albino rats were used.
E, F, G and H vibrissae were measured in mice for the first seven generations
starting after birth.
Fig. 2 shows an illustration of the first seven complete cycles of the F vibrissal
follicle in a male C3H mouse. The first two cycles of vibrissae are smaller than
subsequent cycles. The full adult length is reached in the fourth cycle and remains
52-2
838
L. IBRAHIM AND E. A. WRIGHT
605040-
DO
30-
c
20 H
10
20
50
100
150
200
220
Age (days)
60-|
20
50
100
150
200
220
Age (days)
Fig. 8. The first five successive cycles of the right side E, F, G and H vibrissae of
an albino rat. A, Male; B, female, a, Tip of the vibrissa was broken off when first
observed, s, An irregularity of the growth curve, possibly a technical error, n, Short
late cycle of E vibrissa which could be again a temporary damage to the follicle.
almost constant in the fifth, sixth and seventh cycles. The E, F, G and H
vibrissae of female mice up to 32 months of age were observed (Table 2). In
old age the growth rates and final lengths of vibrissae are little affected but
shortly before death there is a significant diminution (Fig. 7).
Growth of rats and mice vibrissae
839
20 i -
J0
20
30
Days
Fig. 9. Growth curve of an F vibrissa in a male adult C3H mouse compared with
a control F from another C3H male mouse, before, during and after dietary
restriction for 3 days. O, Control F whisker; A, experimental F whisker; # , body
weight of the control mouse; A, body weight of the mouse under dietary restriction;
S, the period of dietary restriction.
(ii) Sex
The E, F, G and H vibrissae were measured in C3H male and female mice
for six generations starting from the first. The first and second generations were
the same length in both sexes. There was no increase in subsequent generations
in females but in males the whiskers were 2-3 mm longer in the third generation
and another 2 mm longer in the fourth, with no further increase in subsequent
generations.
The E, F, G and H vibrissal cycles of male and female rats are shown in Fig. 8.
The patterns of growth in rats are very similar to those seen in mice with the
exception that the length of vibrissae in male rats continues to increase for at
least five cycles. This corresponds to the continued increase in body weight
peculiar to these male rats.
(iii) Plucking
When a new whisker appears above the surface of the skin, plucking the old
resting whisker has no effect on the growth of the new whisker. This is probably
because the new whisker matrix is much deeper in the follicle than the club of
the old whisker. Plucking a growing whisker is followed by a delay of 8-11 days
before a new one appears at the skin surface from the follicle.
Histological examination of the follicle from which a growing whisker has
been plucked shows that a variable proportion of dividing matrix cells is left
behind.
840
L. IBRAHIM AND E. A. WRIGHT
(iv) Dietary restriction
C3H mice were deprived of food for 3 days while their E, F, G and H follicles
were in the anagen phase. The rate of growth was reduced after 1 day of food
deprivation and recovered almost to normal 3 days after return to a full diet
(Fig. 9). The hair did not grow as long as the normal control.
DISCUSSION
(i) Arrangement of vibrissae
We have used Danforth's nomenclature of vibrissae although some investigators (Oliver, 1966; Coultas, 1973) have used different systems of naming the
individual vibrissal follicles. The regularity of this pattern in mice is extremely
constant. In our strains of mice we have occasionally observed that one follicle
fails to produce any vibrissae. This has been seen in less than 1 % of mice.
Dun (1958), using 1-day-old fixed specimens of inbred CBA mice (crossed with
an albino stock), found approximately one vibrissal follicle missing in every
500 observed at birth.
The vibrissae, which include the orbital, post-oral, inter-ramal and ulnar
carpal groups as well as the mystacial groups, are richly supplied with sensory
nerves and are probably as important as sight to these rodents.
(ii) Measurements
Downes & Lyne (1961), Ashmore & Uttley (1965), Priestley (1966), Comaish
(1969) and Jackson & Ebling (1972) used cystine labelled with sulphur-35 and
an autoradiographic method to measure the rate and duration of growth of
body hair in sheep, mice, rats, men and guinea-pigs respectively. The advantages
of our method of direct measurement as compared to autoradiography are its
simplicity and accuracy; also the results are immediately available.
(iii) Normal growth of vibrissae
Dry (1926) divided the phases of hair development into anagen or growing,
catagen when the root decreases in size, and telogen when the hair has become
a club hair and all growth has ceased. We have generally avoided these terms
because anagen is synonymous with the growing period, telogen is synonymous
with the resting period or absence of growth, while catagen represents a period
between anagen and telogen when growth rate is slowing down but in which
we are usually unable to measure the change in size of the root which is the basis
of Dry's classification. Dry also recorded the maximum lengths of vibrissae in
the mouse and observed some of the general growth characteristics.
Fig. 4 A and B and Table 1 show the growth rates, lengths and cycle times
of a selection of vibrissal follicles of various sizes in mice and rats. The resting
period of all follicles is approximately the same. The cycle time of the smaller
Growth of rats and mice vibrissae
841
vibrissal follicles is shorter than that of the larger vibrissal follicles. The rate
of growth of the smallest vibrissae measured (column d) was approximately
one third that of the largest, E, F, G and H. However, the lengths of these small
vibrissae were approximately one quarter the largest and this accounts for the
finding that the cycle times were slightly shorter.
It is a remarkable fact that although the vibrissae progressively increase in
width as they approach full size, they also increase in length by a constant
amount each day throughout most of the growing period (anagen). The constant
increase in length of vibrissae resembles the steady growth of human scalp hair
and wool, although the width of scalp hair and wool change little during most
of the growing period. It is difficult to envisage a control mechanism that
ensures a constant linear growth rate but at the same time permits a progressively
increasing cross-sectional area. Priestley & Rudall (1964) accounted for the
constrictions of zigzag hairs in the albino rat by complementary increase in
the thickness of the Henley layer of the inner root sheath. This mechanism
does not apply to vibrissae because none of the components of the inner root
sheath show any major change in size during the cycle. The layers of Henley,
Huxley and inner root sheath cuticle remain at one cell thickness throughout
the cycle, whereas the hair shaft increases in diameter by a large increase in
the number of the cells of the cortex and medulla.
The diameters of the tips of vibrissae were found to be less than 5 jum and
the widest parts of F vibrissae in the mouse were 90 /im. Inspection of histological preparations at all stages of the hair cycle showed a progressive increase
in number of cortical and medullary cells as the cycle proceeded. There was no
obvious change in the size of the cells.
(iv) Age and sex
Generally the growth rate of vibrissae from any particular follicle remains
constant, and therefore differences in length are accounted for by differences in
the period of growth. Age had little effect on the growth of vibrissae and some
of this might have been due to terminal illness.
Johnson (1958) and Ebling & Johnson (1964) found that male rats have longer
body hair than females. They explained this as due to differences in the rate of
growth. Although we found that male mice and rats have longer vibrissae than
their female counterparts, the rate of growth was almost the same, and the
differences in length were due to differences in the duration of the growth
period.
(v) Plucking
Collins (1918) and David (1934) demonstrated that if hairs are pulled out of
resting follicles activity is induced - that is, a new hair will start growing. Chase
(1955) explained the induction of hair growth after plucking by assuming that an
inhibitor accumulated in the hair follicle during the growth period and that this
842
L. IBRAHIM AND E. A. WRIGHT
gradually dissipated during the resting period. Plucking during the resting stage
removes the inhibitor along with the club hair and so activity recommences.
Bullough (1965) also explained the hair cycles on an inhibitor (chalone) hypothesis. On the other hand, Swann (1958) suggested that plucking released an
inductive stimulus. Johnson & Ebling (1964) plucked rat hairs at intervals
throughout the cycle. Plucking during the resting phase (and before mitotic
activity in the new matrix had begun) resulted in eruption of a new hair 12 days
later. Plucking after mitotic activity in the matrix had begun had no influence
on the expected time of eruption. Plucking at other times during the cycle produced a variable advance or in some cases a retardation of the expected time of
eruption. We have found with vibrissae that plucking during the growth period
resulted in the eruption of a new hair 8-11 days later. Plucking during the
resting phase had no influence on the expected date of eruption of the new
hair.
Johnson and Ebling could not explain their results completely either by the
removal of an inhibitor or by producing an inductive stimulus because of the
variable response to plucking. Our results, however, could be explained in terms
of removal of an inhibitor because plucking the hair always resulted in the growth
of a new vibrissa after a constant period. The differences may be due to the
different types of hair being examined. Yibrissal follicles show almost continuous mitotic activity. If there is a period of quiescent mitotic activity this is
very short and certainly less than 3 days.
(vi) Dietary restriction
Many authors have shown the effects of dietary restriction on hair growth
(Downes & Lyne, 1961; Bradfield & Bailey, 1967; Cabak, Gresham & McCance,
1962). Our contribution illustrates that the effects are produced quickly and
recover equally quickly on return to normal diet (Wright, 1965).
The vibrissal follicle produces hair with outstanding regularity. Each follicle
can be influenced locally and independently of its mirror image on the contralateral side. These features make it a very satisfactory test object.
a—«._i
Growth of rats and mice vibrissae
843
j l j - 3 - J I /*—~»—*
We are pleased to thank Mr G. Harwood for the histological work and photography,
Miss Clare Liddelow for some of the charts and Mrs V. Rivers for typing the manuscript.
Figs. 1, 2 and 9 were published in the Proceedings of the Royal Society of Medicine and are
reproduced by permission.
Some of this work was carried out while E.A.W. was in receipt of U.S.P.H.S. training
grant CRT-508 from the National Cancer Institute, United States Public Health Service.
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{Received 1 August 1974, revised 20 December 1974)