Abstract
Because alternative RNA splicing regulation in the testis is prevalent, we explored testes of Sprague–Dawley rats for existence of alternatively spliced colony-stimulating factor 1 receptor (CSF-1R) mRNA. Using RT-PCR and sequencing, we identified a variant of CSF-1R mRNA that was 284 bp shorter than the full-length CSF-1R transcript. This variant was present in the testis (late fetal stage to adult) and in other organs of rats (7 and 60 days old). The deletion of 284 bp disrupted the open reading frame, resulting in a noncoding mRNA product. When testicular macrophages were stimulated with CSF-1R ligand and lipopolysaccharide, proportionally increased expression of both short isoform and full-length CSF-1R mRNA was observed. Thus, the identified isoform of CSF-1R mRNA may interfere with the expression of full-length CSF-1R mRNA, thereby affecting the biological activity of the ligand/receptor signaling axis in Sprague–Dawley rats.
Similar content being viewed by others
References
Arceci RJ, Shanahan F, Stanley ER, Pollard JW (1989) Temporal expression and location of colony-stimulating factor 1 (csf-1) and its receptor in the female reproductive tract are consistent with csf-1-regulated placental development. Proc Natl Acad Sci USA 86:8818–8822
Arceci RJ, Pampfer S, Pollard JW (1992) Expression of csf-1/c-fms and sf/c-kit mRNA during preimplantation mouse development. Dev Biol 151:1–8
Byrne PV, Guilbert LJ, Stanley ER (1981) Distribution of cells bearing receptors for a colony-stimulating factor (csf-1) in murine tissues. J Cell Biol 91:848–853
Cohen PE, Hardy MP, Pollard JW (1997a) Colony-stimulating factor-1 plays a major role in the development of reproductive function in male mice. Mol Endocrinol 11:1636–1650
Cohen PE, Zhu L, Pollard JW (1997b) Absence of colony-stimulating factor-1 in osteopetrotic (csfmop/csfmop) mice disrupts estrous cycles and ovulation. Biol Reprod 56:110–118
Dai XM, Ryan GR, Hapel AJ, Dominguez MG, Russell RG, Kapp S, Sylvestre V, Stanley ER (2002) Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects. Blood 99:111–120
Elliott DJ, Grellscheid SN (2006) Alternative RNA splicing regulation in the testis. Reproduction 132:811–819
Fuller K, Owens JM, Jagger CJ, Wilson A, Moss R, Chambers TJ (1993) Macrophage colony-stimulating factor stimulates survival and chemotactic behavior in isolated osteoclasts. J Exp Med 178:1733–1744
Guilbert LJ, Stanley ER (1980) Specific interaction of murine colony-stimulating factor with mononuclear phagocytic cells. J Cell Biol 85:153–159
Heid CA, Stevens J, Livak KJ, Williams PM (1996) Real time quantitative PCR. Genome Res 6:986–994
Johnston DS, Jelinsky SA, Zhi Y, Finger JN, Kopf GS, Wright WW (2007) Identification of testis-specific male contraceptive targets: insights from transcriptional profiling of the cycle of the rat seminiferous epithelium and purified testicular cells. Ann NY Acad Sci 1120:36–46
Oatley JM, Oatley MJ, Avarbock MR, Tobias JW, Brinster RL (2009) Colony-stimulating factor 1 is an extrinsic stimulator of mouse spermatogonial stem cell self-renewal. Development 136:1191–1199
Pixley FJ, Stanley ER (2004) Csf-1 regulation of the wandering macrophage: complexity in action. Trends Cell Biol 14:628–638
Pollard JW, Hennighausen L (1994) Colony-stimulating factor 1 is required for mammary gland development during pregnancy. Proc Natl Acad Sci USA 91:9312–9316
Pollard JW, Dominguez MG, Mocci S, Cohen PE, Stanley ER (1997) Effect of the colony-stimulating factor-1 null mutation, osteopetrotic (csfm(op)), on the distribution of macrophages in the male mouse reproductive tract. Biol Reprod 56:1290–1300
Sherr CJ, Rettenmier CW, Sacca R, Roussel MF, Look AT, Stanley ER (1985) The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, csf-1. Cell 41:665–676
Sultana T, Svechnikov K, Weber G, Soder O (2000) Molecular cloning and expression of a functionally different alternative splice variant of prointerleukin-1alpha from the rat testis. Endocrinology 141:4413–4418
Tushinski RJ, Oliver IT, Guilbert LJ, Tynan PW, Warner JR, Stanley ER (1982) Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy. Cell 28:71–81
Wang Y, Berezovska O, Fedoroff S (1999) Expression of colony-stimulating factor-1 receptor (csf-1r) by CNS neurons in mice. J Neurosci Res 57:616–632
Wiktor-Jedrzejczak W, Bartocci A, Ferrante AW Jr, Ahmed-Ansari A, Sell KW, Pollard JW, Stanley ER (1990) Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse. Proc Natl Acad Sci USA 87:4828–4832
Xie Y, Chen C, Hume DA (2001) Transcriptional regulation of c-fms gene expression. Cell Biochem Biophys 34:1–16
Yeung YG, Jubinsky PT, Sengupta A, Yeung DC, Stanley ER (1987) Purification of the colony-stimulating factor 1 receptor and demonstration of its tyrosine kinase activity. Proc Natl Acad Sci USA 84:1268–1271
Acknowledgments
We thank Yvonne Löfgren Blomquist for technical support. This study was supported financially by the Stiftelsen Anna-Brita och Bo Castegrens Minne, the Stiftelsen Samariten, and Sällskapet Barnvård. Hong Su was financially supported by Stiftelsen för Barnendokrinologisk Forskning och Utbildning. Mi Hou received a grant from Svenska Sällskapet för Medicinsk Forskning (SSMF), and Olle Söder was funded by the Swedish Research Council/Finish Academy (VR-FA), the Swedish Research Council (VR), and the Pediatric Cancer Fund (BCF) in Sweden.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Su, H., Wang, Y., Söder, O. et al. Identification of an Isoform of Colony-Stimulating Factor 1 Receptor mRNA in the Rat Testis. Biochem Genet 52, 310–319 (2014). https://doi.org/10.1007/s10528-014-9649-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10528-014-9649-6