NOD mouse model for Sjögren's syndrome: lack of longitudinal stability.
OBJECTIVE
The non-obese diabetic (NOD) mouse is not only a widely used model for diabetes mellitus type I, but also for the chronic autoimmune disease Sjögren's syndrome (SS), mainly affecting salivary and lacrimal glands. We studied the efficacy of local recombinant serotype 2 adeno-associated viral (rAAV2) vector transfer of immunomodulatory transgenes to alter the SS-like disease in NOD mice. Data collected over a 2-year period indicated a changing SS phenotype in these mice and this phenomenon was investigated.


METHODS
10(10) particles rAAV2LacZ/gland were delivered to both submandibular glands (SMGs) of NOD/LtJ mice at 8 weeks (before sialadenitis onset) of age. Salivary flow rates were determined at 8 weeks and time of killing. Blood glucose levels and body weights were measured weekly. After killing, saliva and SMGs were harvested. Analyses of salivary output, inflammatory infiltrates (focus score), SMG cytokine profile, body weight, and diabetes mellitus status were performed. Data from six different experimental studies over 2 years were analyzed and compared.


RESULTS
Salivary flow rate, focus score, and SMG cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12(p70), tumor necrosis factor-alpha and IFNgamma showed changes over time. There were no differences for body weight, diabetes mellitus prevalence, or blood glucose level of non-diabetic mice.


CONCLUSIONS
This retrospective report is the first to describe longitudinal variability in the NOD mouse as a model for SS. We advise other investigators to continuously monitor the SS phenotype parameters and include appropriate controls when studying this disease in NOD mice.
Lodde
B M
BM
Gene Therapy and Therapeutics Branch/NIDCR, NIH, DHHS, Bethesda, MD 20892-1190, USA. blodde@nidcr.nih.gov
Mineshiba
F
F
Kok
M R
MR
Wang
J
J
Zheng
C
C
Schmidt
M
M
Cotrim
A P
AP
Kriete
M
M
Tak
P P
PP
Baum
B J
BJ
D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007763:Lac Operon; D008137:Longitudinal Studies; D051379:Mice; D016688:Mice, Inbred NOD; D010641:Phenotype; D012463:Saliva / Q000378:metabolism; D012636:Secretory Rate; D012859:Sjogren's Syndrome / Q000235:genetics / Q000503:physiopathology*; D013363:Submandibular Gland / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma