Breeding and preliminarily phenotyping of a congenic mouse model with alopecia areata

Mei-Er GU; Xiao-Ming SONG; Chun-Feng ZHU; Hong-Ping YIN; Gui-Jie LIU; Li-Ping YU; Wei-Wei YANG; Li-Feng NI; Yan-Li ZHANG; Bao-Jin WU

doi:10.13918/j.issn.2095-8137.2014.4.249

Volume 35 Issue 4

Jul. 2014

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Article Navigation > Zoological Research > 2014 > 35(4): 249-255

Mei-Er GU, Xiao-Ming SONG, Chun-Feng ZHU, Hong-Ping YIN, Gui-Jie LIU, Li-Ping YU, Wei-Wei YANG, Li-Feng NI, Yan-Li ZHANG, Bao-Jin WU. Breeding and preliminarily phenotyping of a congenic mouse model with alopecia areata. Zoological Research, 2014, 35(4): 249-255. doi: 10.13918/j.issn.2095-8137.2014.4.249

Citation:

Mei-Er GU, Xiao-Ming SONG, Chun-Feng ZHU, Hong-Ping YIN, Gui-Jie LIU, Li-Ping YU, Wei-Wei YANG, Li-Feng NI, Yan-Li ZHANG, Bao-Jin WU. Breeding and preliminarily phenotyping of a congenic mouse model with alopecia areata. Zoological Research, 2014, 35(4): 249-255. doi: 10.13918/j.issn.2095-8137.2014.4.249

Breeding and preliminarily phenotyping of a congenic mouse model with alopecia areata

doi: 10.13918/j.issn.2095-8137.2014.4.249

Laboratory of Experimental Animal Science, Hangzhou Normal University, Hangzhou 310036, China

Received Date: 2013-11-25
Rev Recd Date: 2013-12-25
Publish Date: 2014-07-08

Abstract

In the current study, the alopecia areata gene was introduced into the C57BL/6 (B6) mouse through repeated backcrossing/intercrossing, and the allelic homozygosity of congenic AA^tjmice (named B6.KM-AA) was verified using microsatellites. The gross appearance, growth characteristics, pathological changes in skin, and major organs of B6.KM-AA mice were observed. Counts and proportions of CD4⁺ and CD8⁺ T lymphocytes in peripheral blood were determined by flow cytometry. Results show that congenic B6.KM-AA mice were obtained after 10 generations of backcrossing/intercrossing. B6.KM-AA mice grew slower than B6 control mice and AA skin lesions were developed by four weeks of age. The number of hair follicles was reduced, but hair structures were normal. Loss of hair during disease progression was associated with CD4⁺ and CD8⁺ T lymphocytes infiltration peri-and intra-hair follicles. No pathological changes were found in other organs except for the skin. In the peripheral blood of B6.KM-AA mice, the percentage of CD4⁺ T cells was lower and percentage of CD8⁺ T cells higher than in control mice. These findings indicate that B6.KM-AA mice are characterized by a dysfunctional immune system, retarded development and T-cell infiltration mediated hair loss, making them a promising new animal model for human alopecia areata.
- Alopecia areata,
- Congenic mouse,
- T-lymphocytes,
- CD4,
- CD8

References

[1]	Chen LF, Shi WP, Liu JH, Chen XM, Qin XW, Hao SY, Zheng XG, Shang YL, Wang YF. 2005. A study on infiltrating T-lymphocytic phenotype and Fas expression in skin lesion area of pelade patients. Shanxi Medical Journal, 34(1): 9-11. (in Chinese)
[2]	Freyschmidt-Paul P, Seiter S, Zöller M, König A, Ziegler A, Sundberg JP, Happle R, Hoffmann R. 2000. Treatment with an anti-CD44v10-specific antibody inhibits the onset of alopecia areata in C3H/HeJ mice. Journal of Investigative Dermatology, 115(4): 653-657.
[3]	Huang WN, Hou XZ, Lu HQ, Lu HM, Xu X. 2007. Studies on the relationship between T lymphocyte subtypes and alopecia areata. Southern China Journal of Dermato-Venereology, 14(4): 208-210. (in Chinese)
[4]	Li SR, Wang DP, Lan H, Zang WY, Ge BS, Li JQ, Wang CE, Lu YF, Lu YY, Li RF. 1999. A new mouse mutant gene mapping. Chinese Science Bulletin, 44(7): 50-55. (in Chinese)
[5]	Mao L, Zheng WJ. 2006. Combining comparative genomics with de novo motif discovery to identify human transcription factor DNA-binding motifs. BMC Bioinformatics, 7(Suppl 4): S21.
[6]	McElwee KJ, Boggess D, King LE Jr, Sundberg JP. 1998. Experimental induction of alopecia areata-like hair loss in C3H/HeJ mice using full-thickness skin grafts. Journal of Investigative Dermatology, 111(5): 797-803.
[7]	McElwee KJ, Pickett P, Oliver RF. 1996. The DEBR rat, alopecia areata and autoantibodies to the hair follicle. British Journal of Dermatology, 134(1): 55-63.
[8]	Michie HJ, Jahoda CA, Oliver RF, Johnson BE. 1991. The DEBR rat: an animal model of human alopecia areata. British Journal of Dermatology, 125(2): 94-100.
[9]	McElwee KJ, Hoffmann R. 2002. Alopecia areata-animal models. Clinical and Experimental Dermatology, 27(5): 410-417.
[10]	McElwee KJ, Spiers EM, Oliver RF. 1996. In vivo depletion of CD8⁺ T cells restores hair growth in the DEBR model for alopecia areata. British Journal of Dermatology, 135(2): 211-217.
[11]	Perret C, Wiesner-Menzel L, Happle R. 1984. Immunohistochemical analysis of T-cell subsets in the peribulbar and intrabulbar infiltrates of alopeciaareata. Acta Dermato Venereologica, 64(1): 26-30.
[12]	Peters LL, Robledo RF, Bult CJ, Churchill GA, Paigen BJ, Svenson KL. 2007. The mice as a model for human biology: a resource guide for complex trait analysis. Nature Reviews Genetics, 8(1): 58-69.
[13]	Sundberg JP, Cordy WR, King LE Jr. 1994. Alopecia areata in aging C3H HeJ mice. Journal of Investigative Dermatology, 102(6): 847-856.
[14]	Sundberg JP, Boggess D, Silva KA, McElwee KJ, King LE, Li R, Churchill G, Cox GA. 2003. Major locus on mouse chromosome 17 and minor locus on chromosome 9 are linked with alopecia areata in C3H HeJ mice. Journal of Investigative Dermatology, 120(5): 771-775.
[15]	Sundberg JP, King LE Jr. 1996. Mouse mutations as animal models and biomedical tools for dermatological research. Journal of Investigative Dermatology, 106(2): 368-376.
[16]	Sun J, Silva1 KA, McElwee KJ, King LE Jr, Sundberg JP. 2008. The C3H HeJ mouse and DEBR rat models for alopecia areata: review of preclinical drug screening approaches and results. Experimental Dermatology, 17(10): 793-805.
[17]	Tian M, Xiong YL, Wang WY, Zhang YD. 2004. Kunming rhinos in mice and its molecular genetic. Chinese Science Bulletin, 49(1): 74-80. (in Chinese)
[18]	Wu BJ, Mao HH, Zhu H, Yan ZF, Yang L, Sun Q, Xu XM, Xue ZF, Li HD. 2003. PCR conditions and application of 39 mouse microsatellites. Acta Laboratorium Animalis Scientia Sinica, 11(4): 216-220. (in Chinese)
[19]	Wu BJ, Mao HH, Zeng YM, Yin LJ, Yin XS, Yang WW, Kang XD, Liu GJ, Yu LP, Gu ME, Wu PL. 2009. Fine Mapping and Identifying the Mutation Gene of snthr-^1Bao Scant Hair Mouse. Zoological Research, 30(3): 267-275. (in Chinese)
[20]	Wu BJ, Zeng YM, Mao HH, Yin LJ, Zhu J, Yang W W, Yin XS, Wu PL, Zhang WD. 2010. Mapping of genetic modifiers of Plcd1 in scant hair mice (snthr^-1Bao). Chinese Science Bulletin, 55(35): 4026-4031.
[21]	Zang WQ, Yang X, Wang T, Xuan XY, Li M, Du Y. 2009. Orientation and analysis of Yuyi hairless mice hairless gene mutation point. Journal of Zhengzhou University: Medical Sciences, 44(6): 1144-1145. (in Chinese)

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通讯作者: 陈斌, bchen63@163.com

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Breeding and preliminarily phenotyping of a congenic mouse model with alopecia areata

Laboratory of Experimental Animal Science, Hangzhou Normal University, Hangzhou 310036, China

Received Date: 2013-11-25

Rev Recd Date: 2013-12-25

Publish Date: 2014-07-08

Key words:

Abstract: In the current study, the alopecia areata gene was introduced into the C57BL/6 (B6) mouse through repeated backcrossing/intercrossing, and the allelic homozygosity of congenic AA^tjmice (named B6.KM-AA) was verified using microsatellites. The gross appearance, growth characteristics, pathological changes in skin, and major organs of B6.KM-AA mice were observed. Counts and proportions of CD4⁺ and CD8⁺ T lymphocytes in peripheral blood were determined by flow cytometry. Results show that congenic B6.KM-AA mice were obtained after 10 generations of backcrossing/intercrossing. B6.KM-AA mice grew slower than B6 control mice and AA skin lesions were developed by four weeks of age. The number of hair follicles was reduced, but hair structures were normal. Loss of hair during disease progression was associated with CD4⁺ and CD8⁺ T lymphocytes infiltration peri-and intra-hair follicles. No pathological changes were found in other organs except for the skin. In the peripheral blood of B6.KM-AA mice, the percentage of CD4⁺ T cells was lower and percentage of CD8⁺ T cells higher than in control mice. These findings indicate that B6.KM-AA mice are characterized by a dysfunctional immune system, retarded development and T-cell infiltration mediated hair loss, making them a promising new animal model for human alopecia areata.

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Reference (21)

[1]	Chen LF, Shi WP, Liu JH, Chen XM, Qin XW, Hao SY, Zheng XG, Shang YL, Wang YF. 2005. A study on infiltrating T-lymphocytic phenotype and Fas expression in skin lesion area of pelade patients. Shanxi Medical Journal, 34(1): 9-11. (in Chinese)
[2]	Freyschmidt-Paul P, Seiter S, Zöller M, König A, Ziegler A, Sundberg JP, Happle R, Hoffmann R. 2000. Treatment with an anti-CD44v10-specific antibody inhibits the onset of alopecia areata in C3H/HeJ mice. Journal of Investigative Dermatology, 115(4): 653-657.
[3]	Huang WN, Hou XZ, Lu HQ, Lu HM, Xu X. 2007. Studies on the relationship between T lymphocyte subtypes and alopecia areata. Southern China Journal of Dermato-Venereology, 14(4): 208-210. (in Chinese)
[4]	Li SR, Wang DP, Lan H, Zang WY, Ge BS, Li JQ, Wang CE, Lu YF, Lu YY, Li RF. 1999. A new mouse mutant gene mapping. Chinese Science Bulletin, 44(7): 50-55. (in Chinese)
[5]	Mao L, Zheng WJ. 2006. Combining comparative genomics with de novo motif discovery to identify human transcription factor DNA-binding motifs. BMC Bioinformatics, 7(Suppl 4): S21.
[6]	McElwee KJ, Boggess D, King LE Jr, Sundberg JP. 1998. Experimental induction of alopecia areata-like hair loss in C3H/HeJ mice using full-thickness skin grafts. Journal of Investigative Dermatology, 111(5): 797-803.
[7]	McElwee KJ, Pickett P, Oliver RF. 1996. The DEBR rat, alopecia areata and autoantibodies to the hair follicle. British Journal of Dermatology, 134(1): 55-63.
[8]	Michie HJ, Jahoda CA, Oliver RF, Johnson BE. 1991. The DEBR rat: an animal model of human alopecia areata. British Journal of Dermatology, 125(2): 94-100.
[9]	McElwee KJ, Hoffmann R. 2002. Alopecia areata-animal models. Clinical and Experimental Dermatology, 27(5): 410-417.
[10]	McElwee KJ, Spiers EM, Oliver RF. 1996. In vivo depletion of CD8⁺ T cells restores hair growth in the DEBR model for alopecia areata. British Journal of Dermatology, 135(2): 211-217.
[11]	Perret C, Wiesner-Menzel L, Happle R. 1984. Immunohistochemical analysis of T-cell subsets in the peribulbar and intrabulbar infiltrates of alopeciaareata. Acta Dermato Venereologica, 64(1): 26-30.
[12]	Peters LL, Robledo RF, Bult CJ, Churchill GA, Paigen BJ, Svenson KL. 2007. The mice as a model for human biology: a resource guide for complex trait analysis. Nature Reviews Genetics, 8(1): 58-69.
[13]	Sundberg JP, Cordy WR, King LE Jr. 1994. Alopecia areata in aging C3H HeJ mice. Journal of Investigative Dermatology, 102(6): 847-856.
[14]	Sundberg JP, Boggess D, Silva KA, McElwee KJ, King LE, Li R, Churchill G, Cox GA. 2003. Major locus on mouse chromosome 17 and minor locus on chromosome 9 are linked with alopecia areata in C3H HeJ mice. Journal of Investigative Dermatology, 120(5): 771-775.
[15]	Sundberg JP, King LE Jr. 1996. Mouse mutations as animal models and biomedical tools for dermatological research. Journal of Investigative Dermatology, 106(2): 368-376.
[16]	Sun J, Silva1 KA, McElwee KJ, King LE Jr, Sundberg JP. 2008. The C3H HeJ mouse and DEBR rat models for alopecia areata: review of preclinical drug screening approaches and results. Experimental Dermatology, 17(10): 793-805.
[17]	Tian M, Xiong YL, Wang WY, Zhang YD. 2004. Kunming rhinos in mice and its molecular genetic. Chinese Science Bulletin, 49(1): 74-80. (in Chinese)
[18]	Wu BJ, Mao HH, Zhu H, Yan ZF, Yang L, Sun Q, Xu XM, Xue ZF, Li HD. 2003. PCR conditions and application of 39 mouse microsatellites. Acta Laboratorium Animalis Scientia Sinica, 11(4): 216-220. (in Chinese)
[19]	Wu BJ, Mao HH, Zeng YM, Yin LJ, Yin XS, Yang WW, Kang XD, Liu GJ, Yu LP, Gu ME, Wu PL. 2009. Fine Mapping and Identifying the Mutation Gene of snthr-^1Bao Scant Hair Mouse. Zoological Research, 30(3): 267-275. (in Chinese)
[20]	Wu BJ, Zeng YM, Mao HH, Yin LJ, Zhu J, Yang W W, Yin XS, Wu PL, Zhang WD. 2010. Mapping of genetic modifiers of Plcd1 in scant hair mice (snthr^-1Bao). Chinese Science Bulletin, 55(35): 4026-4031.
[21]	Zang WQ, Yang X, Wang T, Xuan XY, Li M, Du Y. 2009. Orientation and analysis of Yuyi hairless mice hairless gene mutation point. Journal of Zhengzhou University: Medical Sciences, 44(6): 1144-1145. (in Chinese)

Breeding and preliminarily phenotyping of a congenic mouse model with alopecia areata

doi: 10.13918/j.issn.2095-8137.2014.4.249

Abstract

References

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通讯作者: 陈斌, bchen63@163.com

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