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The Near-Naked Hairless (HrN) Mutation Disrupts Hair Formation but Is Not Due to a Mutation in the Hairless Coding Region Yutao Liu, Suchita Das, Robert E. Olszewski, Donald A. Carpenter, Cymbeline T. Culiat, John P. Sundberg, Patricia Soteropoulos, Xiaochen Liu, Mitchel J. Doktycz, Edward J. Michaud, Brynn H. Voy Journal of Investigative Dermatology Volume 127, Issue 7, Pages (July 2007) DOI: /sj.jid Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions
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Figure 1 The phenotype of HrN mutant mice. (a) Hair loss and gross appearance of 13-day-old +/+, HrN/+, and HrN/HrN mice (left-to-right); (b) skin wrinkling in an adult HrN/HrN mouse (5-month-old); vibrissae of +/+, HrN/+, and HrN/HrN mice (left-to-right) at (c) 7 days and (d) 5 weeks of age; (e, f) effect of the HrN mutation on body growth from 7 days to 5 weeks of age; (e) body weight and (f) nose-to-tail length were measured in independent sets of HrN/HrN, HrN/+, and +/+ mice at each time point (n=3–6 per time point). Data were analyzed for significant differences between genotypes using Student's t-test; *P<0.05. Journal of Investigative Dermatology , DOI: ( /sj.jid ) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions
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Figure 2 Light microscopy of hairs from HrN mice. Individual hairs were plucked and examined for gross morphology by light microscopy; (a–d) wild-type; (e–h) HrN/+; (i–l) HrN/HrN; a, b, e, f, i, and j × 4 magnification; c, d, g, h, k, and l × 25 magnification. Journal of Investigative Dermatology , DOI: ( /sj.jid ) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions
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Figure 3 SEM. Sections of dorsal skin were prepared for SEM as described; (a and d) wild-type; (b and e) HrN/+; (c and f) HrN/HrN; bar, a–c=200μm; d–f=20μm. Journal of Investigative Dermatology , DOI: ( /sj.jid ) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions
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Figure 4 Progressive histologic lesions in HrN mice; scale bar in each panel represents 100μm. (a) Changes in HrN/HrN mutant mice were visible as bright eosinophilic areas in the precortex in 3-day-old mice. (b) Normal 7-day-old mice had well-formed late anagen follicles. (c) Heterozygous mice appeared to have normal follicles at 7 days of age although by 9 days of age the normal septated hair fibers underwent abrupt changes and dystrophy (n, double-headed arrow). (d–f) Mutant mice had prominent eosinophilic cells with elongated nuclei in the precortical region at 7 days of age. (e) This change resulted in formation of a thin, deformed fiber with no septation pattern in its medulla. (f, arrows) When the follicle was placed out of focus to focus on the fiber these changes were evident. (g–j; g and h, 2 weeks of age; i, 3 weeks of age; j, 4 weeks of age) The precortical change was associated with formation of a highly deformed fiber to no fiber. (k) In older mice at 5 months of age, follicular cysts with amphophilic regions stained positive for mineralization using a von Kossa stain. (l) Involuting HrN/HrN follicles upon entry into catagen; arrow, apoptosis. (m, double arrows) Masson's trichrome stain revealed normal collagen around small blood vessels and nerves in wild-type and (o, arrow) heterozygous mice. (p, arrow) Occasionally, there were fibrous tracks into the hypodermal fat in heterozygous mice suggesting a follicular scar. (n) Heterozygous hair fibers abruptly became deformed (arrows) above a normal-appearing precortex and follicle region. (q) Homozygous mutant mice formed follicular cysts of uniform size filled with laminated cornified material that when ruptured resulted in a foreign body granuloma with fibrosis. (r–t) Ki67 expression was similar in +/+, HrN/+, and HrN/HrN at 7 days of age although miniaturization of follicles was evident. Journal of Investigative Dermatology , DOI: ( /sj.jid ) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions
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