Alternative titles; symbols
HGNC Approved Gene Symbol: ARTN
Cytogenetic location: 1p34.1 Genomic coordinates (GRCh38) : 1:43,933,801-43,937,240 (from NCBI)
Neurotrophic factors, such as GDNF (600837), NTN (602018), and PSPN (602921), orchestrate multiple aspects of the development and maintenance of the central and peripheral nervous systems. These GDNF family ligands signal though a multicomponent receptor system composed of a high affinity binding component, (GFRA1-GFRA4; see 601496) and a common signaling component, the RET (164761) receptor tyrosine kinase. By searching databases for sequences related to NTN, Baloh et al. (1998) identified human and mouse genomic clones and cDNAs encoding a novel member of the GDNF family, which they named Artemin. Northern blot analysis revealed that Artemin is expressed at low levels in many peripheral adult tissues. Using in situ hybridization analysis of rat embryos at E14, the authors found that Artemin is expressed in regions that are likely to influence the development of peripheral neurons, such as the nerve roots, but not the developing neurons, of the dorsal root ganglia. The predicted human Artemin protein contains a signal peptide and a large proregion. The mature protein contains 113 amino acids.
Baloh et al. (1998) demonstrated that Artemin, like GDNF and NTN, supports the survival of neurons from all peripheral ganglia examined, including sympathetic, neural crest, and placodally derived sensory neurons. In addition, Artemin can support the survival of at least 1 population of central nervous system neurons, the dopaminergic midbrain neurons. Artemin is a ligand for the GFR-alpha-3 (GRFA3; 605710) coreceptor, which together with RET, represents the preferred multicomponent receptor for Artemin signaling.
In a mouse model of neuropathic pain, Gardell et al. (2003) found that systemic, intermittent administration of artemin produced dose- and time-related reversal of nerve injury-induced pain behavior as well as partial to complete normalization of multiple morphologic and neurochemical features of the injury state. After spinal injury, there was an increase in dorsal root ganglion cells that were GFR-alpha-3 reactive, the primary site of artemin action.
Baloh et al. (1998) determined that the Artemin gene contains 3 introns.
By genomic sequence analysis, Baloh et al. (1998) mapped the Artemin gene to chromosome 1p33-p32.
Honma et al. (2002) found that Artn- and Gfra3-deficient mice shared abnormalities in the migration and axonal projection pattern of the entire sympathetic nervous system, resulting in abnormal innervation of target tissues and cell death due to lack of neurotrophic support. They visualized Artn expression in transgenic mice expressing fluorescence-tagged Artn in order to characterize these defects. Fluorescence was detected along blood vessels and in cells nearby to sympathetic axonal projections. Honma et al. (2002) confirmed the chemoattractive properties of Artn by demonstrating that sympathetic neuroblasts migrated and projected axons toward Artn-soaked beads implanted into mouse embryos.
Baloh, R. H., Tansey, M. G., Lampe, P. A., Fahrner, T. J., Enomoto, H., Simburger, K. S., Leitner, M. L., Araki, T., Johnson, E. M., Jr., Milbrandt, J. Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFR-alpha-3-RET receptor complex. Neuron 21: 1291-1302, 1998. [PubMed: 9883723] [Full Text: https://doi.org/10.1016/s0896-6273(00)80649-2]
Gardell, L. R., Wang, R., Ehrenfels, C., Ossipov, M. H., Rossomando, A. J., Miller, S., Buckley, C., Cai, A. K., Tse, A., Foley, S. F., Gong, B., Walus, L., and 10 others. Multiple actions of systemic artemin in experimental neuropathy. Nature Med. 9: 1383-1389, 2003. [PubMed: 14528299] [Full Text: https://doi.org/10.1038/nm944]
Honma, Y., Araki, T., Gianino, S., Bruce, A., Heuckeroth, R. O., Johnson, E. M., Jr., Milbrandt, J. Artemin is a vascular-derived neurotrophic factor for developing sympathetic neurons. Neuron 35: 267-282, 2002. [PubMed: 12160745] [Full Text: https://doi.org/10.1016/s0896-6273(02)00774-2]