Genetic manipulation of CD74 in mouse strains of different backgrounds can result in opposite responses to central nervous system injury.
The ability to recover from CNS injuries is strain dependent. Transgenic mice that weakly express the p41 CD74 isoform (an integral membrane protein functioning as a MHC class II chaperone) on an I-A(b) genetic background have normal CD4(+) T cell populations and normal surface expression of MHC class II, but their B cell development is arrested while the cells are still immature. After a CNS injury, these mice recover better than their matched wild-type controls. We generated p41-transgenic mice on an I-A(d) background (p41-I-A(d) mice), and found that their recovery from CNS injuries was worse than that of controls. A correlative inverse effect was seen with respect to the kinetics of T cell and B cell recruitment to the injured CNS and the expression of insulin-like growth factor at the lesion site. These results, besides verifying previous findings that B cells function in the damaged CNS, demonstrate that the outcome of a particular genetic manipulation may be strain dependent.
Schori
Hadas
H
Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel.
Shechter
Ravid
R
Shachar
Idit
I
Schwartz
Michal
M
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology*; D002490:Central Nervous System / Q000293:injuries* / Q000473:pathology; D002493:Central Nervous System Diseases / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; C474482:I-A(b) antigen, mouse; C111389:I-Ad antigen; D020033:Protein Isoforms; C045084:invariant chain