Disease relevance of Ttc7

• The insertion leads to reduced levels of wild-type Ttc7 transcripts in fsn mice and the insertion of an additional exon derived from the retrovirus into the majority of Ttc7 mRNAs [1].
• The Tetratricopeptide repeat domain 7 gene is mutated in flaky skin mice: a model for psoriasis, autoimmunity, and anemia [1].
• The flaky skin (fsn) mutation in mice causes pleiotropic abnormalities including psoriasiform dermatitis, anemia, hyper-IgE, and anti-dsDNA autoantibodies resembling those detected in systemic lupus erythematosus [1].
• Flaky skin (gene symbol fsn) is an autosomal recessive mutation that causes pleiotropic effects of anemia, papulosquamous skin disorder, and gastric forestomach hyperplasia [2].
• Modulations of the flaky phenotype in response to injury and three different treatments suggest that fsn/fsn is a useful in vivo model for examining new treatment modalities for psoriasiform skin diseases [3].

High impact information on Ttc7

• Neonatal hea mice show a similar hematologic phenotype to the flaky skin (fsn) mutant [4].
• We mapped the hea gene near the fsn locus on mouse chromosome 17 and show that the mutants are allelic [4].
• The decrease in hematocrit levels and red blood cell counts is significant and persists throughout life in fsn/fsn mice [2].
• The fsn/fsn mice examined at 8 weeks of age have significantly increased reticulocyte counts and protoporphyrin levels but reduced hemoglobin concentration, suggesting possible abnormalities of hemoglobin metabolism [2].
• Compared with normal +/? littermates, fsn/fsn mice (1) lack splenic and hepatic stores of elemental iron, (2) have the ability to transport 59Fe across the duodenal cells and into the blood, (3) have increased levels of transferrin in serum, and (4) have acute loss of urinary 59Fe [2].

Chemical compound and disease context of Ttc7

• Autoimmunity in fsn/fsn mice was evidenced by glomerulonephritis accompanied by immune complex deposition in the kidneys, increased serum blood urea nitrogen levels, and the presence of circulating anti-double-stranded DNA autoantibodies [5].

Biological context of Ttc7

• The fsn mutation was mapped to an interval of 3.9 kb on chromosome 17 between D17Mit130 and D17Mit162 [1].
• Homozygotes (fsn/fsn) showed increased size and histological alterations in the spleen and lymph nodes [5].
• We report the discovery of a strong candidate gene affecting iron homeostasis in two allelic anemia mouse mutants: hea (hereditary erythroblastic anemia) and fsn (flaky skin) [6].
• 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 [7].
• 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 [7].

Anatomical context of Ttc7

• The Ttc7 is expressed in multiple types of tissue including skin, kidney, spleen, and thymus, but is most abundant in germinal center B cells and hematopoietic stem cells, suggesting an important role in the development of immune system cells [1].
• In fsn/fsn skin, one sees marked acanthosis and hyperkeratosis with focal parakeratosis, subcorneal pustules, dermal capillary dilation, and a marked diffuse dermal infiltration of mixed inflammatory cells, predominantly lymphocytes [8].
• These results demonstrate a critical pathogenic role of neutrophils for hyperproliferative inflammatory lesions in fsn/fsn mice, suggesting that blocking neutrophil function may have therapeutic benefit in some human skin disorders [9].
• Abnormalities in lymphoid architecture of the spleen in fsn/fsn mice were accompanied by marked increases in total numbers of B cells, macrophages, and immature erythroid cells [5].
• The autosomal recessive mutation "flaky skin" (fsn) causes pleiotropic abnormalities in the immune and hematopoietic systems accompanied by pathologic changes in the skin [5].

Associations of Ttc7 with chemical compounds

• Based on tritiated thymidine uptake, we found DNA synthesis rates elevated threefold or more in fsn/fsn epidermis compared to littermate control mouse skin [8].
• Overall, the results from this study suggest that the helminth immunomodulatory glycan LNFPIII functions to prevent development of psoriatic-like skin lesions in fsn/fsn mice [10].

Other interactions of Ttc7

• Asebia (ab), flaky skin (fsn), and chronic proliferative dermatitis (cpd) are spontaneous mouse mutations with psoriasiform skin alterations of unclear pathogenesis [11].
• Pathogenic function of IL-1 beta in psoriasiform skin lesions of flaky skin (fsn/fsn) mice [12].
• Increased epidermal growth factor receptor in fsn/fsn mice [3].
• Similar to murine models with compromised CD22/SHP-1 function, flaky skin (fsn) mutant mice exhibit lymphocyte hyperactivation and an autoimmune phenotype characterized by circulating autoantibodies to dsDNA and glomerulonephritis [13].
• The production of IL-4 by fsn/fsn T-lymphocytes is increased dramatically compared with normal controls [14].

Analytical, diagnostic and therapeutic context of Ttc7

• EGF-R levels were characterized in unperturbed sites in fsn/fsn skin and +/? skin by enzyme-linked immunosorbent assay, 125I-EGF binding, and immunostaining [3].
• We tested the hypothesis that flaky-skin mice (fsn/fsn), one proposed genetic animal model of psoriasis, would display EGF-R levels comparable to human psoriatic epidermis and show similar biologic responses [3].
• Immunophenotyping of fsn/fsn splenic B cells was performed to determine if abnormalities in CD22 expression contributed to the phenotype [13].

References