Collagen Antibody Induced Arthritis (CAIA)
mouse model for Rheumatoid Arthritis
Introduction
Collagen-induced arthritis (CIA) has been extensively
used as a mouse-model for Rheumatoid Arthritis.
However, it takes 3-5 weeks before the first signs
of inflammation can be identified macroscopically.
To shorten this time interval, ModiQuest Research
has developed a rapid mouse model of Rheumatoid
Arthritis: Collagen Antibody Induced Arthritis (CAIA).
In the MQR-CAIA model, severe arthritis is induced
by i.p. or i.v. injection of a mix of anti-collagen
antibodies; the disease onset can be synchronized by
LPS injection on day 3. The MQR-CAIA model is very
efficient (100% incidence, depending on the mouse
strain used), and ideal for the rapid screening of
novel arthritis therapeutics and to study the
mechanisms involved in the development of arthritis.
The CAIA antibodies can be delivered directly to
clients for in-house animal model generation.
Alternatively, complete animal studies are offered by
ModiQuest Research.
Figure 1) Mice were injected i.p. with 2.6mg CAIA antibody
mixture and followed during 7 days. Pictures were taken 3 days
after LPS injection.
1-2 Swollen Toes 3-4 Swollen toes
Slightly Swollen footpad or ankle
Swollen Footpad or Ankle with
Swollen Footpad or Ankle + 1-2 Swollen Toes
Swollen Footpad + Swollen Ankle + Swollen Toes
Table 1) Arthritis scoring method
Collagen-induced arthritis
Collagen-induced arthritis is an antibody
mediated disease. Therefore, type II collagen
specific antibodies can be used to induce arthritis
in mice. ModiQuest Research’s mixture of type II
collagen specific antibodies induces severe inflammation in the ankles and paws of DBA/ J1 mice
(Figure 1, 2), which resemble many aspects of
arthritis. One of the biggest advantages of our
monoclonal antibody-induced arthritis model is that
arthritis is induced within 24-72 hours (Figure 3)
instead of the four weeks required to induce arthritis
after immunization with type II collagen. ModiQuest
Research recommends highly susceptible DBA/ J1
mice. Other mouse strains may be used as well, however the amount of antibody cocktail required may
vary.
MQR-CAIA model:
Specifications:
Reagents provided: Mixture of 8 antibodies that
recognize 7 different collagen type II epitopes
(Isotypes: IgG1, IgG2a, IgG2b)
0.25
0.50
0.50-0.75
1.00
1.25-1.50
2.00
Procedure:
1) On day 0, administer antibody
cocktail intra peritoneal (i.p.)
between 2.4 mg and 3.2 mg
per animal.
2) In-between day 3 and 7, LPS can
be administered i.p. (25μg/
animal) to enhance and
synchronize the inflammation
3) Observe arthritis score throughout
the study on a daily basis. Initial
symptoms of arthritis typically
appear on day 2 (Table 1)
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Figure 2) DBA/ J1 mice were
treated i.p. with MQR-CAIA
mix (2.3 mg total). A control
antibody (CTL) was used at the
same concentration. LPS (25
ug/ mouse) was injected i.p.
on day 7.
Pictures are histological preparations of hind paws 25 days
after anti-collagen antibody
injection.
SO Safranin-O staining
(blue indicates bone,
red indicates cartilage)
HE HaematoxylinEosin staining
* inflammatory infiltrate
Use of the CAIA model to test anti-inflammatory agents for Rheumatoid Arthritis therapy
Dose specific efficacy of anti-inflammatory agents
was demonstrated in the CAIA mouse model for
Rheumatoid Arthritis. Three days following i.p.
injection of the CAIA mix in DBA/ J1 mice,
inflammation was induced and synchronized
by LPS injection. In a typical efficacy experiment,
the
first
signs
of
inflammation
are
observed on day 5 (Figure 4).
Animals receiving no anti-inflammatory agent
developed maximum inflammation at day 9. A single
prophylactic administration of an anti-inflammatory
antibody (co-injected at the time of LPS induction)
prevents the inflammatory response altogether.
3,2 mg
90
% Incidence
B
Arthritis Incidence
100
Total Arthritis Score/group
A
2,4 mg
80
0,8 mg
70
CTL 2,3mg
60
50
40
30
20
10
0
0
2
4
6
Daily
administration
of
dexamethasone
during the onset of inflammation temporarily
represses the inflammation (administration from day 6,
approximately halfway the maximum inflammatory
response, through day 9, when the inflammation
is fully repressed). Immediately after dexamethasone administration is lifted, inflammation is quickly
restored at approximately half its maximum value.
Prolonged daily administration of dexamethasone
fully represses the inflammation (data not shown).
8
10
12
Days
14
16
18
20
22
Total Arthritis Score
25
20
15
10
5
0
0
2
4
6
8
10
12
Days
14
16
18
20
22
Figure 3) CAIA using 8 monoclonal antibodies. Arthritis incidence (A) and total arthritis score (B) are indicated. Groups of 6 DBA/
J1 mice were treated i.p. with MQR-CAIA mix. Different concentrations of the antibody cocktail (0.8 mg, 2.4 mg, and 3.2 mg)
were used. A control antibody (CTL) was used at a 2.3 mg concentration. LPS (25 μg/ mouse) was injected i.p. on day 7.
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Figure 4) Effect of dexamethasone and an antiinflammatory antibody in a
CAIA experiment. The therapeutic application of dexamethasone in the CAIA
model (applied daily from
day 6 through 9) represses
the inflammation for the
duration of its administration. The mean arthritis score
upon prophylactic administration of an anti-inflammatory antibody (on day 3,
at the time of inflammation
induction) shows a prolonged
inflammation-repressing
effect.
In conclusion
The ModiQuest Research advantage
We have generated and validated a Collagen
Antibody Induced Arthritis (CAIA) mouse model for
Rheumatoid Arthritis. Using this CAIA model, the
efficacy of anti-inflammatory agents can be tested
upon prophylactic and therapeutic administration,
within a time frame of three weeks.
ModiQuest Research specializes in the generation
of human and animal antibodies against difficult
targets, such as posttranslational modifications. We
also perform feasibility studies, pilot studies, and
technology development projects for antibodies or
antibody-producing cell lines. Through our web shop,
we sell newly developed antibodies and assays for
use in research, diagnostics, and animal models.
MQR-CAIA model:
Advantages:
• Set of 8 thoroughly evaluated anti-collagen
antibodies in one CAIA Cocktail Mix
• LPS synchronization of inflammation onset
simplifies treatment schedule
• i.p. injection instead of i.v. injection
• Easy and ready to use mouse model with high
sensitivity
• Incidence rates as high as 100%, which allows for
a smaller size of animal groups
• CAIA Cocktail Mix reduces the experimental
time span
• Ideal for rapid screening and evaluation of antiinflammatory therapeutic agents
ModiQuest Research: ‘Discover Your Potential’
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[email protected]