Flaky Skin (fsn) Mutant Mouse Chr17

The flaky skin mutant mouse arose spontaneously in the A/J inbred strain at The Jackson Laboratory in 1985. Mutant mice were severely runted with thick scaly skin and were difficult to maintain. A congenic strain was created, using ovarian transfer technology, by crossing A/J with BALB/cByJ mice to produce a more viable strain for investigation of the psoriasiform dermatitis that these mice develop. This new congenic strain, Cby.A-fsn/J, is readily available for study from The Jackson Laboratory mutant mouse repository (JR# 001723). A second allele, the Hereditary Erythroblastic Anemia (hea) mouse, arose spontaneously in Japan. The mutation was mapped to the distal end of Chr. 17 and it was recently identified as a novel gene the function of which has yet to be determined.
Mutant and littermate control mice can not be differentiated by skin lesions until the time of weaning when mutant mice develop thick white scales associated with patchy alopecia. The dorsal skin has patchy alopecia and scaling while the ventral skin develops a fine scale and banding pattern of thinning hair. The skin develops progressively worsening alopecia and scaling with age. Mutant mice are mildly anemic at birth (pale) which makes it possible to identify them before skin lesions are obvious. As the mice age, they develop a pendulous abdomen due to a marked enlargement of their spleens. While gross skin lesions raise concerns about infectious processes, such as dermatophytes (ringworm), these mice were raised and studied under specific pathogen free conditions and routinely tested for all known mouse pathogens and none were involved in the phenotype.
Histologically, skin of flaky skin mutant mice is thick at birth as is the case for wildtype mice of all strains. By 2 weeks of age the epidermis normally thins to only a few layers. Flaky skin mutant mouse skin thins slightly at 2 weeks then becomes progressively thicker eventually stabilizing in thickness. This is associated with an increase in production of epithelial cells as determined by bromodeoxyuridine and tritiated thymidine uptake studies. Mutant mice develop marked acanthosis and orthokeratotic hyperkeratosis with focal parakeratotic mounds. In the A/J strain there is essentially no stratum granulosum, as is the case with many human cases of psoriasis. The BALB congenic strain develops hypergranulosis with lesion progression, a change considered inconsistent with most forms of human psoriasis. In the dermis capillaries are dilated and there is a mixed inflammatory cell infiltrate. This was mostly neutrophils (based on myloperoxidase levels) in A/J mutant mice but predominantly mononuclear cells in the BALB congenic. Gene expression studies revealed the response to be predominantly Th2 in contrast to most human psoriasis cases that are Th1.
A variety of other organs are affected by this mutation. One of the most notable being the forestomach. Papillomatous hyperplasia reaches an extreme to the point of essentially occluding the lumen of the stomach.


Sundberg JP; Kenty GA; Beamer WG; Adkison DL, Forestomach papillomas in flaky skin and steel-Dickie mutant mice., J Vet Diagn Invest 1992 Jul;4(3):312-7

Sundberg JP; Boggess D; Sundberg BA; Beamer WG; Shultz LD, Epidermal dendritic cell populations in the flaky skin mutant mouse., Immunol Invest 1993 Jul;22(5):389-401

Sundberg JP; Boggess D; Shultz LD; Beamer WG, The flaky skin (fsn) mutation, Chromosome ?, In: Handbook of Mouse Mutations with Skin and Hair Abnormalities: Animal Models and Biomedical Tools. Sundberg, JP (ed.), CRC Press, Boca Raton, FL, pp 253-268, 1994

Sundberg JP; Dunstan RW; Roop DR; Beamer WG, Full-thickness skin grafts from flaky skin mice to nude mice: maintenance of the psoriasiform phenotype., J Invest Dermatol 1994 May;102(5):781-8

Pelsue SC; Schweitzer PA; Beamer WG; Shultz LD, Mapping of the flaky skin (fsn) mutation on distal mouse chromosome 17 (Errata; Mamm Genome 1996; 7:92.), Mamm Genome 1995 Oct;6(10):758

Beamer WG; Pelsue SC; Shultz LD; Sundberg JP; Barker JE, The flaky skin (fsn) mutation in mice: map location and description of the anemia., Blood 1995 Oct 15;86(8):3220-6

Morita K; Hogan ME; Nanney LB; King LE Jr; Manabe M; Sun TT; Sundberg JP, Cutaneous ultrastructural features of the flaky skin (fsn) mouse mutation., J Dermatol 1995 Jun;22(6):385-95

Nanney LB; Sundberg JP; King LE, Increased epidermal growth factor receptor in fsn/fsn mice., J Invest Dermatol 1996 Jun;106(6):1169-74

Sundberg JP; France M; Boggess D; Sundberg BA; Jenson AB; Beamer WG; Shultz LD, Development and progression of psoriasiform dermatitis and systemic lesions in the flaky skin (fsn) mouse mutant., Pathobiology 1997;65(5):271-86

Sundberg JP; Sundberg BA; Beamer WG, Comparison of chemical carcinogen skin tumor induction efficacy in inbred, mutant, and hybrid strains of mice: Morphologic variations of induced tumors and absence of a papillomavirus cocarcinogen., Mol Carcinog 1997 SEP;20(1):19-32

Sundberg JP ; Beamer WG ; Shultz LD, Lymphadenopathy, elevated serum IgE levels, autoimmunity, and mast cell accumulation in flaky skin mutant mice., Eur J Immunol 1998 Apr;28(4):1379-88

Schon MP, Animal models of psoriasis - what can we learn from them? [see comments], J Invest Dermatol 1999 Apr;112(4):405-10

Abernethy NJ; Hagan C; Tan PL; Watson JD, Dysregulated expression of CD69 and IL-2 receptor alpha and beta chains on CD8+ T lymphocytes in flaky skin mice., Immunol Cell Biol 2000 Dec;78(6):596-602

Schon M; Denzer D; Kubitza RC; Ruzicka T; Schon MP, Critical role of neutrophils for the generation of psoriasiform skin lesions in flaky skin mice., J Invest Dermatol 2000 May;114(5):976-83

Schon M; Behmenburg C; Denzer D; Schon MP, Pathogenic function of IL-1 beta in psoriasiform skin lesions of flaky skin (fsn/fsn) mice., Clin Exp Immunol 2001 Mar;123(3):505-10

White RA; McNulty SG; Roman S; Garg U; Wirtz E; Kohlbrecher D; Nsumu NN; Pinson D; Gaedigk R; Blackmore K; Copple A; Rasul S; Watanabe M; Shimizu K, Chromosomal localization, hematologic characterization, and iron metabolism of the hereditary erythroblastic anemia (hea) mutant mouse., Blood 2004 Sep 1;104(5):1511-8

Sundberg JP. Skin and Adnexa of the Laboratory Mouse. In: Handbook of Experimental Animals: The Laboratory Mouse. Hedrich, HJ (ed.), Academic Press, London, pp. 195-206, 2004.

Back to Top