The Relationship Between Hyperproliferation and Epidermal Thickening in a Mouse Model for BCIE  Rebecca M. Porter, Julia Reichelt, Declan P. Lunny, Thomas M. Magin, E. Birgitte Lane  Journal of Investigative Dermatology  Volume 110, Issue 6, Pages 951-957 (June 1998) DOI: 10.1046/j.1523-1747.1998.00218.x Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Morphologic changes occuring in the epidermis of different body sites in the mice heterozygous for the keratin 10 truncation. (a) Wild-type back epidermis of adult mice is very thin with a single layer of suprabasal cells. (b) Heterozygous back epidermis usually showed mild acanthosis and hyperkeratosis. (c) Wild-type ear epidermis is also thin with only one or two cell layers in the suprabasal epidermis. (d) Ear epidermis of heterozygotes was increased in thickness, showing both severe acanthosis and hyperkeratosis. (e) Paw epidermis of wild-type mice shows a thick suprabasal layer and stratum corneum. (f) Paw epidermis in heterozygotes is increased in thickness with generally larger cells in the stratum granulosum. The stratum corneum is irregular and hyperkeratotic. (g) Snout epidermis is slightly thicker than back epidermis with two layers in the suprabasal layer. (h) Heterozygous snout shows severe acanthosis of the stratum spinosum and stratum granulosum with a large increase in cell layers in the stratum corneum. Scale bar, 50 μm. Journal of Investigative Dermatology 1998 110, 951-957DOI: (10.1046/j.1523-1747.1998.00218.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Morphology of the esophagus and forestomach. (a) The esophagus of a wild-type mouse. (b) Esophagus of a heterozygous animal showing both acanthosis and hyperkeratosis. (c) Forestomach of wild-type mouse. (d) Forestomach of heterozygous mouse. Scale bar, 100 μm. Journal of Investigative Dermatology 1998 110, 951-957DOI: (10.1046/j.1523-1747.1998.00218.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Immunohistochemistry of markers for proliferation. Ki67 antigen was detected in a large number of nuclei in heterozygous ear (b) compared with very few labeled nuclei in the wild-type ear (a). Very few BrdU labeled nuclei were also detected in wild-type ear (c) but a significant increase is observed in heterozygous ear epidermis (d). PCNA was detected in a large number of basal and suprabasal cells in the heterozygous ear (f) but was confined to a small number of basal cells in the wild-type epidermis (e). Arrows indicate examples of positive nuclei in the basal cell layer of the epidermis in each photograph. Scale bar, 50 μm. Journal of Investigative Dermatology 1998 110, 951-957DOI: (10.1046/j.1523-1747.1998.00218.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Immunofluorescence of mouse epidermis using antibodies to keratins. High levels of K16 (a) and K6 (b) are expressed in the epidermis of heterozygous tail samples. Double immunofluorescence on the same section as (b) shows that K2e (c) is expressed in heterozygous adult tail epidermis in cells that also express K6. K6 (d) and K16 (e) are upregulated in some regions of the ear of heterozygous animals. In the snout, K6 was induced in regions in close proximity to the hair follicles (f), whereas K16 was more generally induced in the suprabasal epidermis (g). Scale bar, 50 μm. Journal of Investigative Dermatology 1998 110, 951-957DOI: (10.1046/j.1523-1747.1998.00218.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions