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As an alternative, the current study utilized non\u2010invasive magnetic resonance imaging (MRI) microscopy and optical spectroscopy to define biophysical characteristics of skin in an animal model of OI. MRI of skin harvested from control, homozygous <jats:italic>oim\/oim<\/jats:italic> and heterozygous <jats:italic>oim<\/jats:italic>\/+ mice demonstrated several differences in anatomic and biophysical properties. Fourier transform infrared imaging spectroscopy (FT\u2010IRIS) was used to interpret observed MRI signal characteristics in terms of chemical composition. Differences between wild\u2010type and OI mouse skin included the appearance of a collagen\u2010depleted lower dermal layer containing prominent hair follicles in the <jats:italic>oim\/oim<\/jats:italic> mice, accounting for 55% of skin thickness in these. The MRI magnetization transfer rate was lower by 50% in this layer as compared to the upper dermis, consistent with lower collagen content. The MRI transverse relaxation time, T2, was greater by 30% in the dermis of the <jats:italic>oim\/oim<\/jats:italic> mice compared to controls, consistent with a more highly hydrated collagen network. Similarly, an FT\u2010IRIS\u2010defined measure of collagen integrity was 30% lower in the <jats:italic>oim\/oim<\/jats:italic> mice. We conclude that characterization of phenotypic differences between the skin of OI and wild\u2010type mice by MRI and FT\u2010IRIS is feasible, and that these techniques provide powerful complementary approaches for the analysis of the skin phenotype in animal models of disease. 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