Reconstitution of Severe Combined Immunodeficient (SCID) Mice with Cetacean Lymphocytes as a Model to Study Immune Functions in Cetaceans
Sylvain De Guise; David A. Ferrick
Department of Pathology, Microbiology and Immunology, School of Veterinary
Medicine, University of California Davis, Davis, CA
Abstract
Mice homozygous for the severe combined immunodeficiency (SCID) mutation
lack functional T and B lymphocytes and fail to generate either humoral or cell-mediated
immunity. The lack of antigen-specific immunity also allows SCID mice to accept allografts and
xenografts. Immune system from several species, including human, rats, cats, cows, horses and
pigs, were reconstituted with increasing amount of success into SCID mice. SCID mice models have
been used for studying the pathogenesis of some diseases as well as for experimental treatments
of diseases like cancer.
Considering that ethical and technical constraints limit the range of
experimental immunological studies that can be performed in live cetaceans, there is a need for
establishing in vivo models in experimental animals that as closely as possible resemble the
cetacean immune system. In a pilot study, SCID mice were reconstituted with 20 x 106
killer whale peripheral blood mononuclear celis (PBMC) or with either 20 x 106 or 100
x 106 splenocytes from a bottlenose dolphin. Mice were sacrificed four weeks after
reconstitution and spleen and blood were sampled and analyzed for the presence of dolphin B and T
lymphocytes using flow cytometry. Dolphin T lymphocytes were found in spleen from one out of 3
mice reconstituted with 100 x 106 splenocytes and in blood of one out of two mice
reconstituted with killer whale PBMC, one out of three mice reconstituted with 20 x 106
splenocytes and in two out of three reconstituted with 100 x 106 splenocytes. Dolphin
B lymphocytes were found only in blood from one out of three mice reconstituted with 20 x
106 splenocytes.
Cetacean-reconstituted SCID nice represents an attractive model for the study
of the physiology of cetacean immune response as well as the pathophysiology of naturally
occurring infectious diseases in captive and wild animals, in addition to represent a unique
opportunity to test the efficacy of vaccination programs not only through the production of
antigen-specific immunoglobulins but also by testing the level of protection through challenges
with the pathogens. A cetacean-SCID model would also allow to address the potential effects of
exposure to pollutants on the immune system of cetaceans.