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Murine "viable motheaten" mutation reveals a gene critical to the development of both B and T lymphocytes
C L Sidman1, J D Marshall, R D Allen
1Jackson Laboratory, Bar Harbor, ME 04609.
Abstract:
In lethally irradiated normal mice reconstituted with both normal and autoimmune mutant viable motheaten (mev) bone marrow, the mev-derived B and T cells display aberrant behavior, while those derived from the normal bone marrow develop and function normally. The observed developmental abnormalities of mev B and T lymphocytes are therefore intrinsic to these cell types, rather than being determined by defective influences from the cells' environment. These data bring into question the in vivo significance of reported intercellular regulatory defects in motheaten (me) and mev mice and suggest that these mutations affect a gene whose product acts cell autonomously in the development of several hematopoietic cell lineages including B and T lymphocytes.
Insights
The autoimmune mutant viable motheaten (mev) mutation causes intrinsic defects in B and T lymphocyte development. These cells show abnormal behavior, indicating the mutation affects a gene critical for hematopoietic cell development.
Area of Science:
- Immunology
- Hematology
- Genetics
Background:
- The motheaten (me) and viable motheaten (mev) mouse models exhibit autoimmune disorders.
- Previous studies suggested intercellular regulatory defects in these models.
Purpose of the Study:
- To investigate the intrinsic versus environmental factors influencing B and T lymphocyte development in mev mice.
- To determine the cellular basis of developmental abnormalities in mev lymphocytes.
Main Methods:
- Bone marrow transplantation experiments in lethally irradiated normal mice.
- Reconstitution with both normal and mev bone marrow.
- Analysis of B and T lymphocyte development and function.
Main Results:
- mev-derived B and T cells showed aberrant behavior and development.
- Normal bone marrow-derived cells developed and functioned normally within the same environment.
- These findings indicate cell-intrinsic defects in mev lymphocytes.
Conclusions:
- The developmental abnormalities in mev B and T lymphocytes are intrinsic to these cell types.
- The study questions the in vivo relevance of previously reported intercellular regulatory defects.
- The mutation likely affects a gene product acting cell-autonomously in hematopoietic development.