Disease relevance of FOXN1

• Ancestral founder mutation of the nude (FOXN1) gene in congenital severe combined immunodeficiency associated with alopecia in southern Italy population [1].
• In addition, WHN gene expression may identify not only thymomas but also epidermoid differentiation in mediastinal and pulmonary tumors [2].
• WHN mRNA could be detected in all thymoma subtypes (n = 14) and epidermoid thymic carcinomas as well as in all squamous cell carcinomas of the lung (n = 5) investigated, but was totally absent in all other mediastinal tumors (n = 11) lacking an epidermoid differentiation [2].

High impact information on FOXN1

• Human Nude/SCID (severe combined immunodeficiency) is the first severe combined immunodeficiency caused by mutation of the winged-helix-nude (WHN) gene, which is expressed in the thymus but not in the hematopoietic lineage [3].
• After an initial recovery, lymphocyte proliferation to mitogens progressively declined compared with controls and genotypically identical donor cells grown in the WHN(+/-) environment [3].
• Recently, several forkhead genes have been demonstrated to play critical roles in lymphocyte development and effector function, including Foxp3 in the development of regulatory T cells, Foxj1 and Foxo3a in the regulation of CD4+ T cell tolerance, and Foxn1 in thymic development [4].
• We show that almost all thymic epithelial cells in the early thymus anlagen express Foxn1, and Dll4 and CCL25 are limitedly expressed in Foxn1-positive epithelial cells [5].
• These results indicate that in the post-natal thymus, epithelial cells may maintain the expressions of those functional molecules without the aid of Foxn1 transcription factor [5].

Biological context of FOXN1

• Genetic alterations of the FOXN1 transcription factor, selectively expressed in thymic epithelia and skin, are responsible in both mice and humans for the Nude/SCID phenotype [1].
• To confirm the ancestral origin of the mutation we genotyped two microsatellite markers, D17S2187 and D17S1880, flanking the FOXN1 gene on chromosome 17 [1].
• Here, we identified and characterized the FOXN5 gene, a novel member of FOXN gene family, by using bioinformatics [6].
• The recently isolated human WHN gene has been previously assigned to chromosome 17q11-12 using radiation hybrids [7].
• We also identified a new mononucleotide polymorphism contained within the untranslated exon 1 of the WHN gene, which may be useful for linkage and LOH studies [7].

Anatomical context of FOXN1

• On the other hand, the expression of Foxn1 was not detectable in a large number of post-natal thymic epithelial cells [5].

Associations of FOXN1 with chemical compounds

• By ordering known and novel markers, we determined the position of the WHN gene, and of the closely linked retinal 4 and sodium/dicarboxylate cotransporter genes [7].

Regulatory relationships of FOXN1

• Both Foxn1-positive and -negative epithelial cells seem to express Dll4 and CCL25 [5].

Other interactions of FOXN1

• FOXN4 and FOXN1 showed 41.3% total-amino-acid identity [8].
• Accumulating expression profile data suggest that CHES1 plays a role in tumorigenicity and responses to cancer treatments, though nothing is known regarding the transcriptional function of CHES1 or other FOXN proteins in human cells [9].
• Expression of Dll4 and CCL25 in Foxn1-negative epithelial cells in the post-natal thymus [5].

Analytical, diagnostic and therapeutic context of FOXN1

• We used the RT-PCR technique for the detection of WHN transcripts in normal human organs and various mediastinal tumors, including various subtypes of thymic epithelial tumors [2].

References