Morphologic and Phenotypic Analysis of an Outcross Line of Blotchy Mouse

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Abstract
Blotchy is an X-linked recessive mutation at the Mottled locus in the mouse. The affected blotchy male (Blo/Y) mouse from an inbred genetic background demonstrates morphologic and physiologic abnormalities consistent with emphysema in adult life. Breeding of Blo/Y mice was difficult because the inbred Blo/Y males are sterile. The successful development of a line of outbred Blo/Y male and Blo/Blo female mice by the controlled outcross mating of the inbred heterozygous Blo/+ female with the Argonne hybrid B6CF1 male mouse is reported. The subsequent outcross Blo/Y progeny breed vigorously with the outcrossed Blo/+ female. The lungs of the outbred Blo/Blo female and inbred Blo/Y male mice demonstrate mild to moderate panacinar emphysema with a significant decrease in internal surface area (P < 0.005) and an increase in mean linear intercept (P < 0.005). The lungs of the outbred Blo/Y is structurally normal. Despite the absence of emphysema-like changes in the oubred Blo/Y males, there were phenotypic features that suggest inherited abnormalities in connective tissus proteins including high incidence of aortitis leading to premature death from aneurysmal rupture, and significant decrease in the morphometrically determined parenchymal elastic fiber length in the lung (P < 0.01). The oubred blotchy strain may be a useful experimental animal model in determining the pathogenesis of emphysema.