Mouse major histocompatibility complex and lung development: haplotype variation, H-2 immunolocalization, and progressive maturation.
The association of the mouse major histocompatibility complex (H-2), lung maturation, and corticosteroid responsiveness has recently been demonstrated in congenic B10 (H-2b) and B10.A (H-2a) mice (Hu et al.: American Journal of Medical Genetics 35:126-131, 1990). We have investigated additional haplotypes [B10.BR (H-2k) and B10.D2 (H-2d)] to confirm that there is a strong association between H-2 haplotype variation and the degree of pulmonary maturation. Lungs of B10.D2, B10.BR, B10, and B10.A congenic mice achieve haplotypic specific maturation: B10.D2 lungs greater than B10 lungs = B10.BR lung greater than B10.A lungs. It appears that the expression of these developmental potentials is under corticosteroid regulation. Further, to test the hypothesis that H-2 antigens would be expressed earlier in embryonic lungs with the H-2b (B10) or H-2k (B10.BR) haplotype than with the H-2a (B10.A) haplotype, we investigated the spatiotemporal patterns of H-2 antigen localization in B10, B10.BR, and B10.A congenic mouse strains with and without corticosteroid treatment. The spatial patterns of H-2 antigen localization was similar in the B10, B10.BR, and B10.A mouse lungs; however, these patterns appeared earlier in both untreated and treated B10 and B10.BR mice as compared with untreated B10.A mice, suggesting an H-2 haplotype associated rate of pulmonary maturation. Following corticosteroid treatment, all congenic strains had a temporally comparable spatial distribution of H-2 antigens. Our results provide preliminary evidence suggesting that both a lung "developmental gene(s)" and a "glucocorticoid responsiveness gene(s)" are most likely outside the K-D subregions of the H-2 complex. A model of the H-2 regulation of lung maturation and corticosteroid responsiveness is discussed.
Jaskoll
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Graduate Program in Craniofacial Biology, University of Southern California Dental School, Los Angeles 90089-0641.
Hu
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Melnick
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D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D005314:Embryonic and Fetal Development / Q000276:immunology; D005260:Female; D005455:Fluorescent Antibody Technique; D006183:H-2 Antigens / Q000032:analysis*; D006239:Haplotypes / Q000235:genetics*; D008168:Lung / Q000187:drug effects / Q000196:embryology* / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D012127:Respiratory Distress Syndrome, Newborn / Q000235:genetics*; D014222:Triamcinolone Acetonide / Q000031:analogs & derivatives / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D006183:H-2 Antigens; D014222:Triamcinolone Acetonide; C005900:triamcinolone hexacetonide