A mutant mouse with severe anemia and skin abnormalities controlled by a new allele of the flaky skin (fsn) locus.

We found a novel recessive mutation in an inbred strain, INT, that was derived from an ICR closed colony. Mice homozygous for this mutation are identified by severe anemia, dysgenesis and neonatal death. This mutation was tentatively named int. Intercrosses of int heterozygotes (+/int) and the flaky skin heterozygotes (+/fsn) resulted in abnormal mice (int/fsn heterozygotes) showing anemia and flaky skin with the expected frequency for autosomal recessive mutation. The int gene was therefore named fsn(Jic) as an allele of the fsn locus on chromosome 17. We carried out phenotype analyses using B6.INT- fsn(Jic) mice to observe phenotypes of blood and skin in the embryonic and neonatal stages. Discrimination of fsn(Jic) embryos from normal embryos was performed by an indirect diagnosis of the fsn(Jic) gene using the D17Mit130 microsatellite marker tightly linked to the fsn locus. The number of fetal nucleated RBC of normal embryos decreased gradually to 17.5 dpc, but that of the abnormal embryos decreased to 14.5 dpc followed by a gradual increase to 17.5 dpc. Skin of fsn(Jic) embryos did not show any abnormalities and expressed cytokeratins normally as skin epithelial cell markers at each embryonic stage (15.5 dpc to 18.5 dpc). Time differences in the appearance of the different phenotypes observed in various tissue and organs of fsn homozygotes suggest they are caused by expression of the fsn gene at different developmental stages.

Atrichia with papular lesions resulting from mutations in the rhesus macaque (Macaca mulatta) hairless gene.

Atrichia with papular lesions (APL) is a rare form of hair loss with an autosomal recessive mode of inheritance that is characterized by the absence of normal hair follicles, and formation of intradermal cystic structures. Mutations in the hairless (hr) gene in mice and humans have been implicated in the development of this phenotype. Hairless is a putative transcription factor containing a single zinc-finger DNA binding domain, with restricted expression in brain and skin. Here, we describe the complete hr cDNA sequence from the rhesus macaque (Macaca mulatta) and report the identification of a compound heterozygous mutation in a hairless rhesus macaque born from unrelated parents. Cutaneous biopsy samples from the affected macaque revealed abnormalities, including the replacement of normal hair follicles with dermal cysts and comedones, reminiscent of the skin phenotype observed in hairless mice and humans with APL.

Multiple pigmented cutaneous papules associated with a novel canine papillomavirus in an immunosuppressed dog.

Cutaneous papillomavirus infection was diagnosed in a 6-year-old female Boxer dog that was under long-term corticosteroid therapy for atopic dermatitis. Multiple black, rounded papules were present on the ventral skin. Spontaneous regression occurred within 3 weeks after cessation of corticosteroids. Histologically, the lesions consisted of well-demarcated cup-shaped foci of epidermal endophytic hyperplasia with marked parakeratosis. In the upper stratum spinosum and in the stratum granulosum, solitary or small collections of enlarged keratinocytes were observed with basophilic intranuclear inclusion bodies and a single eosinophilic fibrillar cytoplasmic inclusion. Ultrastructurally, viruslike particles (40-45 nm in diameter) were observed within the nucleus, free or aggregated in crystalline arrays. Undulating fibrillar material, thought to be a modified keratin protein, was observed in the cytoplasmic inclusion. Immunohistochemistry, restriction enzyme analysis, and molecular hybridization experiments indicated that these distinctive clinical, histologic, and cytologic features were associated with a novel canine papillomavirus.