IsletTransplant - UCSF Animal Care and Use Program

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INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC)
IACUC / LARC STANDARD PROCEDURES
ISLET TRANSPLANTATION UNDER THE KIDNEY CAPSULE IN MICE (May 2007)
Description of procedure:
Islet Transplantation (following the NIH recommended procedure): Islets are obtained from the
pancreas of euthanized donor mice that have been cervically dislocated. Donor mice will not be
euthanized with CO2 prior to cervical dislocation because of the change in blood and tissue pH
due to the CO2 exposure. It has been shown that islet beta cell function and enzymes used to
locate the islet beta cells are sensitive to pH changes. Only personnel who have sufficient
experience with conscious mice will carry out the cervical dislocation of the donor mice.
Mice will be firmly restrained and quickly euthanized. A mid-line incision is then made and the
diaphragm is cut. The donor pancreas can then be removed for isolation of the beta islets.
The recipient mice are anesthetized and pre-operative analgesics are administered. The
surgical area of the mouse will be shaved and cleaned with iodine or chlorhexidine solution and
aseptic techniques practiced. A small incision is made in the left flank and the left kidney is
exposed. Approximately 500-1000 islets are transplanted under the kidney capsule using a
Hamilton syringe with P-150 polypropylene tubing. Hemostasis is maintained, the tissue is
moistened with saline and the kidney is placed back into the abdominal cavity. The peritoneum
is then closed with 5-0 silk sutures and the skin is closed with surgical glue or wound clips.
Antibiotics may be indicated for diabetic or immuno-compromised animals. The mouse is
allowed to recover in the cage with a heat lamp or heat pad, under close supervision. If surgical
clips are used, they are removed 10-14 days post surgery. Transplanted mice will be followed
until rejection or 100 days at which time the mice will be euthanize.
Mice will be evaluated for general appearance, ability to move normally around cage and reach
food and water, ability to eat and drink, grooming habits, skin color, lethargy, aggression
(animals will be housed individually if aggressive behavior is shown). Mice will be evaluated by
the Body Condition scoring index. Mice will be monitored continuously after anesthesia until
ambulatory. Mice are then monitored daily for the first 3-5 days and weekly thereafter. Mice with
Body Condition score < 2 will be euthanized.
Literature search words required:
Literature search was performed for refinement of this Standard Procedure on April 9, 2007
Key Words
Search Site
Years
Covered
Islet transplantation in rodents
Pubmed
1968-2007
Agents:
Anesthestics, antibiotics, analgesics
This procedure requires, general anesthesia (local anesthesia recommended) and systemic
analgesics. Immuno-compromised animals may receive antibiotics. All agents administered to
animals should be listed in the "Agents" section of RIO.
Adverse Effects:
Procedure, Agent or Potential Adverse
Phenotype
Effects
Management
Kidney capsule
grafting
Kidney capsule
grafting
Rejection
Euthanasia
Infection
Consult LARC
veterinarian
Monitoring Parameters:
Monitoring
Parameters
Frequency
General
appearance/activity
level
Body condition
scoring
Daily for first 3-5 days No
and then weekly
thereafter
Daily for first 3-5 days No - unless indicated
and then weekly
thereafter
Daily for first 3-5 days No
and then weekly
thereafter
Examine incision
PI/Lab will Document
Describe the conditions, complications, and criteria (e.g. uncontrolled
infection, loss of more than 15% body weight, etc.) that would lead to removal
of an animal from the study, and describe how this will be accomplished (e.g.
stopping treatment, euthanasia).
Euthanasia criteria: BCS < 2; significant surgical dehiscence or other incision
problems that cannot be managed with veterinary care.
For all investigators housing animals with tumor formation, skin lesions,
neurological deficits, or that are in Category E, list the expected
characteristics/clinical presentations and endpoints of the animal model and
the criteria for euthanasia. Note: The IACUC also requires such lists to be
posted in the respective animal rooms and monitored by the IACUC
compliance staff and LARC, to assure PI adherence to the endpoints listed.
N/A
Updated 5/2007
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