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.
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