Disease relevance of Arnt2

• Either stably or transiently expressed Arnt/Arnt2 wild type and various mutants or chimeric constructs in Hepa1-c4 cells exhibit similar levels of hypoxic response element-driven reporter gene expression and the induction of endogenous Glut-1 through binding with HIFalpha in response to hypoxia [1].
• The expression and predicted functions of many of these genes provide new insight into both the Sim1/Arnt2 action in neuroendocrine hypothalamus development and the molecular basis for the Sim1 haplo-insufficient obesity phenotype [2].

High impact information on Arnt2

• Targeted mutation of the murine arylhydrocarbon receptor nuclear translocator 2 (Arnt2) gene reveals partial redundancy with Arnt [3].
• In addition, cultured Arnt2(-/-) neurons display decreased hypoxic induction of HIF-1 target genes, demonstrating formally that ARNT2/HIF-1alpha complexes regulate oxygen-responsive genes [3].
• 5. These results demonstrate that Arnt and Arnt2 have both unique and overlapping essential functions in embryonic development [3].
• cDNA cloning and tissue-specific expression of a novel basic helix-loop-helix/PAS factor (Arnt2) with close sequence similarity to the aryl hydrocarbon receptor nuclear translocator (Arnt) [4].
• Expression of Arnt2 successfully rescued XRE-driven reporter gene activity in the Arnt-defective c4 mutant of Hepa-1 cells [4].

Biological context of Arnt2

• Although Arnt2 is a candidate for the thymus defects in c112K homozygotes, the possibility that other as yet unidentified genes in the c112K deletion are responsible for the abnormalities has not been ruled out [5].
• In contrast, we observed clear functional differences in the ability of Arnt and Arnt2 to induce xenobiotic response element-driven reporter and endogenous CYP1A1 gene expression [1].
• Taken together, our results demonstrate that Arnt2 is an indispensable transcription factor for the development of the hypothalamus, and suggest that Arnt2 is an obligatory partner molecule of Sim1 in the developmental process of the neuroendocrinological cell lineages [6].

Anatomical context of Arnt2

• In addition, whole-mount in situ hybridization of 9.5-day mouse embryos showed that Arnt2 mRNA was expressed in the dorsal neural tube and branchial arch 1, while Arnt transcripts were detected broadly in various tissues of mesodermal and endodermal origins [4].
• We subsequently generated germ line Arnt2 mutant mice by gene targeting technology [6].

Associations of Arnt2 with chemical compounds

• Biochemical properties and interaction of Arnt2 with other bHLH/PAS proteins were investigated by coimmunoprecipitation assays, gel mobility shift assays, and the yeast two-hybrid system [4].

Other interactions of Arnt2

• These results suggest that Arnt2 may play different roles from Arnt both in adult mice and in developing embryos [4].
• Similar to full-length Sim2, Sim2s interacts with Arnt and to a lesser extent, Arnt2 [7].
• Sim1, Arnt2, and Otp genes are essential for terminal differentiation of these neurons [8].

References