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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0801406v1 183/4/2529    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Meek, K. Articles by Georges, G. PubMed PubMed Citation Articles by Meek, K. Articles by Georges, G.

SCID Dogs: Similar Transplant Potential but Distinct Intra-Uterine Growth Defects and Premature Replicative Senescence Compared with SCID Mice¹

Katheryn Meek^2,*, Ari Jutkowitz, Lisa Allen, Jillian Glover^*, Erin Convery^*, Alisha Massa^*, Tom Mullaney^*, Bryden Stanley, Diana Rosenstein, Susan M. Bailey, Cheri Johnson and George Georges

^* Department of Pathobiology and Diagnostic Investigation, and Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University; East Lansing, MI 48824; Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523; and Fred Hutchinson Cancer Research Center, Seattle, WA 98109

We have previously described DNA-dependent protein kinase (DNA-PKcs) mutations in horses and dogs that result in deficits in V(D)J recombination, DNA repair, and SCID. In this paper, we document substantial developmental growth defects in DNA-PKcs-deficient dogs that are not apparent in SCID mice. Fibroblast cell strains derived from either fetal or adult SCID dogs proliferate poorly in culture and undergo premature replicative senescence, somewhat reminiscent of cells derived from Ku-deficient mice. A limited number of animals have been immune reconstituted (by bone marrow transplantation) so that they can be maintained in a normal environment for long periods. Several of these animals have developed conditions associated with premature ageing at 2–3 years of age, roughly 20% of their expected lifespan. These conditions include intestinal malabsorption and primary neural cell neoplasia. These results suggest that DNA-PKcs deficiency is not tolerated equally in all species, perhaps providing insight into why DNA-PKcs deficiency has not been observed in humans. Finally, this study demonstrates the feasibility of maintaining SCID dogs for extended periods of time and documents their utility for bone marrow transplantation studies and as hosts for the propagation of xenografts. In sum, SCID dogs may present researchers with new possibilities for the development of animal models of human disease.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Public Health Service Grant RR016537 (K.M.).

² Address correspondence and reprint requests to Dr. Katheryn Meek, Michigan State University, 350 FST, East Lansing, MI 48824. E-mail address: kmeek{at}msu.edu

³ Abbreviations used in this paper: DNA-PKcs, DNA-dependent protein kinase, catalytic subunit; DLA, dog leukocyte Ag; NHEJ, nonhomologous DNA end joining.

⁴ The online version of this article contains supplemental material.