Disease relevance of Alx3

• Compound mutants of Alx3 and Alx4, however, show severe craniofacial abnormalities that are absent in Alx4 single mutants [1].

High impact information on Alx3

• Alx3/Alx4 double mutant newborn mice have cleft nasal regions [1].
• We have generated an Alx3 mutant allele in which the lacZ coding sequence is inserted in-frame in the Alx3 gene and the sequences encoding the conserved protein domains are deleted [1].
• We found that Alx3 is coexpressed with insulin in pancreatic islets, as well as in the beta-cell line MIN6, and it is also present in glucagon- and somatostatin-expressing cells [2].
• Thus, these studies support the notion that Alx3 participates in the regulation of insulin gene expression in pancreatic beta-cells [2].
• Alx3 was localized to chromosome 3, near the droopy-ear (de) mutation [3].

Biological context of Alx3

• Alx3 is expressed in mouse embryos from 8 days of gestation onward in a characteristic pattern, predominantly in neural crest-derived mesenchyme and in lateral plate mesoderm [3].
• The Alx3 protein contains a divergent aristaless domain that appears not to be functional, as ectopic expression of Alx3 results in an altered phenotype irrespective of the presence of this aristaless domain [4].
• Severe nasal clefting and abnormal embryonic apoptosis in Alx3/Alx4 double mutant mice [1].

Anatomical context of Alx3

• Chromatin immunoprecipitation assays indicated that Alx3 present in MIN6 cells and in mouse pancreatic islets occupies the promoter of the mouse insulin genes [2].

Other interactions of Alx3

• Linking the Cart1 aristaless domain to Alx3 extinguishes teratogenicity [4].
• Prior to this defect, both Alx3 and Alx4 were specifically down regulated in the most ventral part of the primary body wall in Hoxb4(PolII) mutants [5].

References