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Motheaten, an immunodeficient mutant of the mouse. I. Genetics and pathology
Abstract:
A new recessive mutation, motheaten (me), is on chromosome 6, 21.9 +/- 4.3 recombination units distal to white (Miwh). Mice homozygous for the new mutation have neutrophilic lesions of the skin beginning as early as day 1, and pneumonitis with many macrophages in the alveoli as early as day 3. They suffer high mortality from birth onward and none has survived longer than 8 weeks. The lymph nodes may be enlarged, but the thymus, Reyer's patches, and lymphatic tissue of the spleen are much reduced in size. Lymph nodes, spleen, and Peyer's patches lack lymphatic nodules. The lymph nodes and spleen contain many plasma cells. There are increased numbers of neutrophils and monocytes in the peripheral blood, and increased numbers of neutrophils in bone marrow at the expense of red cell precursors. Hematopoietic tissue in the spleen is increased and appears more active than normal. Motheaten mice appear to have an immune deficiency beginning very shortly after birth.
Insights
A new mutation called motheaten causes severe immune deficiency in mice. This genetic mutation leads to skin lesions, lung inflammation, and high mortality, impacting immune cell development and function.
Area of Science:
- Immunology
- Genetics
- Developmental Biology
Background:
- A novel recessive mutation, designated motheaten (me), has been identified.
- This mutation is located on chromosome 6, distal to the white (Miwh) locus.
Purpose of the Study:
- To characterize the phenotypic effects of the motheaten mutation in mice.
- To investigate the immunological consequences of this mutation.
Main Methods:
- Phenotypic analysis of homozygous motheaten mice from birth.
- Histopathological examination of lymphoid organs and tissues.
- Hematological analysis of peripheral blood and bone marrow.
Main Results:
- Homozygous motheaten mice exhibit early-onset neutrophilic skin lesions and pneumonitis.
- High mortality rates are observed from birth, with no survival beyond 8 weeks.
- Significant reduction in thymus, Peyer's patches, and spleen lymphatic tissue; lymph nodes may be enlarged.
- Peripheral blood shows increased neutrophils and monocytes; bone marrow has increased neutrophils at the expense of red cell precursors.
- Spleen displays increased and hyperactive hematopoietic tissue.
Conclusions:
- The motheaten mutation confers a severe, early-onset immune deficiency in mice.
- The mutation affects multiple aspects of the immune system, including lymphoid organ development and hematopoiesis.
- Motheaten mice serve as a model for studying congenital immune deficiencies.