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Anti-interferon immunoglobulins can improve the trisomy 16 mouse phenotype
1Department of Medical Microbiology/Immunology, Southern Illinois University School of Medicine, Springfield 62794, USA.
Abstract:
Mouse trisomy 16 is a well-studied model for human chromosome 21 trisomy (Down's syndrome). The late stage trisomy 16 mouse fetus exhibits significant growth retardation, inappropriately opened eyes, and convex rather than concave back curvature. The interferons (alpha, beta, and gamma) have potent growth retarding activity, and sensitivity to these cytokines is controlled by genes that map to mouse chromosome 16 and human chromosome 21. In experiments designed to determine if the interferons induce or aggravate the trisomy phenotype, mice pregnant with trisomy 16 fetuses were injected with a combination of anti-alpha, -beta, and -gamma interferon IgG. This maternal anti-interferon treatment was found to provide measurable benefit to the development and growth of the trisomic fetuses with significant return-toward-normal values observed for overall fetal growth, eye opening, and back curvature.
Insights
Maternal treatment with anti-interferon antibodies improved development in trisomy 16 mouse fetuses, a model for Down syndrome. This suggests interferons contribute to trisomy-related growth and developmental issues.
Area of Science:
- Genetics
- Developmental Biology
- Immunology
Background:
- Mouse trisomy 16 (Ts16) serves as a model for human chromosome 21 trisomy (Down syndrome).
- Ts16 fetuses display growth retardation, developmental abnormalities like premature eye opening, and altered spinal curvature.
- Interferons (IFNs) exhibit growth-retarding properties, and IFN sensitivity is linked to genes on mouse chromosome 16 and human chromosome 21.
Purpose of the Study:
- To investigate the role of interferons (alpha, beta, gamma) in the trisomy 16 phenotype.
- To determine if blocking interferons can ameliorate developmental defects in Ts16 fetuses.
Main Methods:
- Mice pregnant with Ts16 fetuses were administered a combination of anti-IFN-alpha, -beta, and -gamma IgG antibodies.
- Evaluated fetal growth, eye opening, and back curvature in treated and untreated Ts16 fetuses.
Main Results:
- Maternal anti-interferon treatment significantly improved overall fetal growth in Ts16 fetuses.
- The treatment also led to a return toward normal values for eye opening and back curvature.
- These findings indicate a beneficial effect of blocking interferons on trisomy-related developmental issues.
Conclusions:
- Interferons likely contribute to or aggravate the developmental phenotype observed in trisomy 16 mice.
- Targeting interferons may offer a therapeutic strategy to mitigate developmental abnormalities associated with Down syndrome.