Alternative titles; symbols
HGNC Approved Gene Symbol: CNTFR
Cytogenetic location: 9p13.3 Genomic coordinates (GRCh38): 9:34,551,433-34,590,852 (from NCBI)
Davis et al. (1991) used the 'tagged-ligand panning' procedure to clone a receptor for ciliary neurotrophic factor (118945). This receptor is expressed exclusively in the nervous system and skeletal muscle. The CNTF receptor was found to have a structure unrelated to the receptors utilized by the nerve growth factor family of neurotrophic molecules, but instead is most homologous to the receptor for a cytokine, interleukin-6 (IL6; 147620). This similarity suggested that the CNTF receptor, like the IL6 receptor, requires a second, signal-transducing component. In contrast to all known receptors, the CNTF receptor is anchored to cell membranes by a glycosyl-phosphatidylinositol linkage.
Valenzuela et al. (1995) found that the human and mouse CNFTR genes have an identical intron/exon structure that correlates well with the domain structure of the protein. The signal peptide and the immunoglobulin-like domain are each encoded by a single exon, the cytokine receptor-like domain is distributed among 4 exons, and the C-terminal glycosylphosphatidylinositol recognition domain is encoded by the final coding exon. The position of the introns within the cytokine receptor-like domain corresponds to that found in other members of the cytokine receptor superfamily.
Donaldson et al. (1993) mapped the CNTFR gene to chromosome 9 by PCR on a panel of human/CHO somatic cell hybrids and regionalized the assignment to 9p13 by PCR on a panel of radiation hybrids.
By fluorescence in situ hybridization, Valenzuela et al. (1995) mapped the CNTFR gene to 9p13, and by interspecific backcross linkage analysis, they mapped the gene to mouse chromosome 4 in a region of known homology of synteny to 9p. By interspecific backcross linkage analysis, Pilz et al. (1995) mapped the Cntfr gene to mouse chromosome 4.
Although mice that are homozygous for an inactivated CNTF gene develop normally and initially thrive and only later in adulthood exhibit very mild loss of motor neurons with resulting minor muscle weakness, DeChiara et al. (1995) found that mice homozygous for 'knockout' of the CNTFR gene died perinatally and displayed severe motor neuron deficits. Thus, the authors concluded that CNTFR is critical for the developing nervous system, most likely by serving as a receptor for a second, developmentally important, CNTF-like ligand.
Using in situ peroxidase and immunofluorescence staining in mouse hearts, Raju et al. (2006) localized Cntf receptors to the sarcolemma and confirmed the localization by immunoblot on isolated myocytes. Subcutaneous administration of recombinant CNTF in mice deficient in leptin (ob/ob; see 164160) and the leptin receptor (db/db; see 601007) resulted in significant reductions in cardiac hypertrophy. Western blotting showed that both leptin and CNTF activated STAT3 (102582) and ERK1 (MAPK3; 601795)/ERK2 (MAPK1; 176948) pathways in cultured adult mouse cardiomyocytes and cardiac tissue from ob/ob and db/db mice. Raju et al. (2006) concluded that CNTF plays a role in a cardiac signal transduction pathway that regulates obesity-related left ventricular hypertrophy.
Davis, S., Aldrich, T. H., Valenzuela, D. M., Wong, V., Furth, M. E., Squinto, S. P., Yancopoulos, G. D. The receptor for ciliary neurotrophic factor. Science 253: 59-63, 1991. [PubMed: 1648265] [Full Text: https://doi.org/10.1126/science.1648265]
DeChiara, T. M., Vejsada, R., Poueymirou, W. T., Acheson, A., Suri, C., Conover, J. C., Friedman, B., McClain, J., Pan, L., Stahl, N., Ip, N. Y., Kato, A., Yancopoulos, G. D. Mice lacking the CNTF receptor, unlike mice lacking CNTF, exhibit profound motor neuron deficits at birth. Cell 83: 313-322, 1995. [PubMed: 7585948] [Full Text: https://doi.org/10.1016/0092-8674(95)90172-8]
Donaldson, D. H., Britt, D. E., Jones, C., Jackson, C. L., Patterson, D. Localization of the gene for the ciliary neurotrophic factor receptor (CNTFR) to human chromosome 9. Genomics 17: 782-784, 1993. [PubMed: 8244400] [Full Text: https://doi.org/10.1006/geno.1993.1409]
Pilz, A., Woodward, K., Povey, S., Abbott, C. Comparative mapping of 50 human chromosome 9 loci in the laboratory mouse. Genomics 25: 139-149, 1995. [PubMed: 7774911] [Full Text: https://doi.org/10.1016/0888-7543(95)80119-7]
Raju, S. V. Y., Zheng, M., Schuleri, K. H., Phan, A. C., Bedja, D., Saraiva, R. M., Yiginer, O., Vandegaer, K., Gabrielson, K. L., O'Donnell, C. P., Berkowitz, D. E., Barouch, L. A., Hare, J. M. Activation of the cardiac ciliary neurotrophic factor receptor reverses left ventricular hypertrophy in leptin-deficient and leptin-resistant obesity. Proc. Nat. Acad. Sci. 103: 4222-4227, 2006. [PubMed: 16537512] [Full Text: https://doi.org/10.1073/pnas.0510460103]
Valenzuela, D. M., Rojas, E., Le Beau, M. M., Espinosa, R., III, Brannan, C. I., McClain, J., Masiakowski, P., Ip, N. Y., Copeland, N. G., Jenkins, N. A., Yancopoulos, G. D. Genomic organization and chromosomal localization of the human and mouse genes encoding the alpha receptor component for ciliary neurotrophic factor. Genomics 25: 157-163, 1995. [PubMed: 7774913] [Full Text: https://doi.org/10.1016/0888-7543(95)80121-2]