The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Meek, K.
Right arrow Articles by Bell, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Meek, K.
Right arrow Articles by Bell, T.
The Journal of Immunology, 2001, 167: 2142-2150.
Copyright © 2001 by The American Association of Immunologists

SCID in Jack Russell Terriers: A New Animal Model of DNA-PKcs Deficiency1

Katheryn Meek2,*, Laura Kienker{dagger}, Clarissa Dallas*, Wei Wang*, Michael J. Dark*, Patrick J. Venta*, Maryann L. Huie{ddagger}, Rochelle Hirschhorn{ddagger} and Tom Bell*

* College of Veterinary Medicine and Department of Veterinary Pathology, Michigan State University, East Lansing, MI 48824; {dagger} Department of Internal Medicine, Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390; and {ddagger} Department of Medicine, New York University Medical Center, New York, NY 10016

We recently described the incidence of a SCID disease in a litter of Jack Russell terriers. In this study, we show that the molecular defect in these animals is faulty V(D)J recombination. Furthermore, we document a complete deficit in DNA-dependent protein kinase activity that can be explained by a marked diminution in the expression of the catalytic subunit DNA-dependent protein kinase catalytic subunit (DNA-PKcs). We conclude that as is the case in C.B-17 SCID mice and in Arabian SCID foals, the defective factor in these SCID puppies is DNA-PKcs. In mice, it has been clearly established that DNA-PKcs deficiency produces an incomplete block in V(D)J recombination, resulting in "leaky" coding joint formation and only a modest defect in signal end ligation. In contrast, DNA-PKcs deficiency in horses profoundly blocks both coding and signal end joining. Here, we show that although DNA-PKcs deficiency in canine lymphocytes results in a block in both coding and signal end joining, the deficit in both is intermediate between that seen in SCID mice and SCID foals. These data demonstrate significant species variation in the absolute necessity for DNA-PKcs during V(D)J recombination. Furthermore, the severity of the V(D)J recombination deficits in these three examples of genetic DNA-PKcs deficiency inversely correlates with the relative DNA-PK enzymatic activity expressed in normal fibroblasts derived from these three species.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
S. Yotsumoto, K. Saegusa, and Y. Aramaki
Endosomal Translocation of CpG-Oligodeoxynucleotides Inhibits DNA-PKcs-Dependent IL-10 Production in Macrophages
J. Immunol., January 15, 2008; 180(2): 809 - 816.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
P. Douglas, X. Cui, W. D. Block, Y. Yu, S. Gupta, Q. Ding, R. Ye, N. Morrice, S. P. Lees-Miller, and K. Meek
The DNA-Dependent Protein Kinase Catalytic Subunit Is Phosphorylated In Vivo on Threonine 3950, a Highly Conserved Amino Acid in the Protein Kinase Domain
Mol. Cell. Biol., March 1, 2007; 27(5): 1581 - 1591.
[Abstract] [Full Text] [PDF]

Home page
 Vet PatholHome page
R. Seymour, J. P. Sundberg, and H. HogenEsch
Abnormal lymphoid organ development in immunodeficient mutant mice.
Vet. Pathol., July 1, 2006; 43(4): 401 - 423.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
R. Dip and H. Naegeli
More than just strand breaks: the recognition of structural DNA discontinuities by DNA-dependent protein kinase catalytic subunit
FASEB J, May 1, 2005; 19(7): 704 - 715.
[Abstract] [Full Text] [PDF]

Home page
 Vet PatholHome page
L. E. Perryman
Molecular Pathology of Severe Combined Immunodeficiency in Mice, Horses, and Dogs
Vet. Pathol., March 1, 2004; 41(2): 95 - 100.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Q. Ding, Y. V. R. Reddy, W. Wang, T. Woods, P. Douglas, D. A. Ramsden, S. P. Lees-Miller, and K. Meek
Autophosphorylation of the Catalytic Subunit of the DNA-Dependent Protein Kinase Is Required for Efficient End Processing during DNA Double-Strand Break Repair
Mol. Cell. Biol., August 15, 2003; 23(16): 5836 - 5848.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
S. Rooney, F. W. Alt, D. Lombard, S. Whitlow, M. Eckersdorff, J. Fleming, S. Fugmann, D. O. Ferguson, D. G. Schatz, and J. Sekiguchi
Defective DNA Repair and Increased Genomic Instability in Artemis-deficient Murine Cells
J. Exp. Med., March 3, 2003; 197(5): 553 - 565.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
T. Woods, W. Wang, E. Convery, A. Errami, M. Z. Zdzienicka, and K. Meek
A single amino acid substitution in DNA-PKcs explains the novel phenotype of the CHO mutant, XR-C2
Nucleic Acids Res., December 1, 2002; 30(23): 5120 - 5128.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2001 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2001 by The American Association of Immunologists, Inc. All rights reserved.