Cell-extrinsic defective lymphocyte development in Lmna(-/-) mice.
BACKGROUND
Mutations in the LMNA gene, which encodes all A-type lamins, result in a variety of human diseases termed laminopathies. Lmna(-/-) mice appear normal at birth but become runted as early as 2 weeks of age and develop multiple tissue defects that mimic some aspects of human laminopathies. Lmna(-/-) mice also display smaller spleens and thymuses. In this study, we investigated whether altered lymphoid organ sizes are correlated with specific defects in lymphocyte development.


RESULTS
Lmna(-/-) mice displayed severe age-dependent defects in T and B cell development which coincided with runting. Lmna(-/-) bone marrow reconstituted normal T and B cell development in irradiated wild-type recipients, driving generation of functional and self-MHC restricted CD4(+) and CD8(+) T cells. Transplantation of Lmna(-/-) neonatal thymus lobes into syngeneic wild-type recipients resulted in good engraftment of thymic tissue and normal thymocyte development.


CONCLUSIONS
Collectively, these data demonstrate that the severe defects in lymphocyte development that characterize Lmna(-/-) mice do not result directly from the loss of A-type lamin function in lymphocytes or thymic stroma. Instead, the immune defects in Lmna(-/-) mice likely reflect indirect damage, perhaps resulting from prolonged stress due to the striated muscle dystrophies that occur in these mice.
Hale
J Scott
JS
Department of Immunology, University of Washington, Seattle, Washington, United States of America.
Frock
Richard L
RL
Mamman
Sara A
SA
Fink
Pamela J
PJ
Kennedy
Brian K
BK
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D034904:Lamin Type A / Q000172:deficiency* / Q000235:genetics; D008214:Lymphocytes / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D009136:Muscular Dystrophies; D013601:T-Lymphocytes / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology
D034904:Lamin Type A
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