Genetic and immunological factors interact in a mouse model of CNS antiphospholipid syndrome.
The antiphospholipid syndrome (APS) includes systemic and central nervous system (CNS) pathology associated with antibodies to a complex of phospholipids and beta(2)-glycoprotein I (beta(2)-GPI). We have recently reported the induction of APS associated with behavioral and cognitive deficits in BALB/c female mice that developed 4-5 months after immunization with beta(2)-GPI. In the present study, we examined the influence of genetic factors on the ability to induce experimental APS with CNS involvement by testing several mouse strains immunized with beta(2)-GPI. Female mice from five strains were immunized once with beta(2)-GPI in complete Freund's adjuvant (CFA) or with CFA alone (controls). Autoantibody levels were examined at 1 and 5 months after immunization. Neurological assessment in a staircase test was performed 4-5 months following the immunization. Induction of APS resulted in elevated levels of antibodies against negatively charged phospholipids and beta(2)-GPI in all five mouse strains. Autoantibody levels were significantly higher in Balb/c, ICR, and C57BL/6 mouse strains compared to AKR and C3H. aPL levels dropped significantly more in the C57BL/6 compared to Balb/c mice over a period of 4 months. Hyperactivity reflected by higher number of stairs climbed in 3 min, was induced by APS in the Balb/c and ICR, mouse strains. Exploratory behavior reflected by more frequent rears, was seen in the APS-Balb/c and AKR mice. Hypoactivity and less exploration were seen in the APS-C57BL/6 and C3H mice. The study supports a link between high levels of aPL and behavioral changes in a mouse APS model. Qualitative differences in behavioral patterns may be due to nervous system as well as immune genetic factors. The minimal effect of APS in C57BL/6 mice may provide a suitable background for the study of transgenes in these mice.
Katzav
Aviva
A
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel. katzava@post.tau.ac.il
Litvinjuk
Yulia
Y
Pick
Chaim G
CG
Blank
Miri
M
Shoenfeld
Yehuda
Y
Sirota
Pinhas
P
Chapman
Joab
J
D000704:Analysis of Variance; D000818:Animals; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000235:genetics* / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis; D001522:Behavior, Animal; D002493:Central Nervous System Diseases / Q000150:complications / Q000235:genetics* / Q000276:immunology*; D003072:Cognition Disorders / Q000209:etiology / Q000276:immunology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage; D051379:Mice; D008815:Mice, Inbred Strains; D011597:Psychomotor Performance / Q000502:physiology; D013045:Species Specificity; D013997:Time Factors; D053482:beta 2-Glycoprotein I
D001323:Autoantibodies; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I