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Gene Review

Rln1  -  relaxin 1

Mus musculus

Synonyms: Prorelaxin 1, Rln, Rlx, rlx
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Disease relevance of Rln1

  • Rln1-knockout mice show progressive tissue fibrosis as they age, and this fibrosis leads to functional changes in both the heart and lungs [1].
  • Rln1 knockout mice exhibit abnormal nipple development, prolonged parturition, agerelated pulmonary fibrosis, and abnormalities in the testes and prostate [2].
  • Functional expression of mouse relaxin and mouse relaxin-3 in the lung from an Ebola virus glycoprotein-pseudotyped lentivirus via tracheal delivery [3].
  • Studies in RLX-deficient mice (Rlx-/-) demonstrate that although females give birth to live young without apparent dystocia, the pubic symphysis is not elongated, and they have abnormal cervical and vaginal morphology [4].
  • Cardiac hypertrophy, evidenced by increased heart weight and expression of hypertrophy-related genes (all P < 0.05 vs. sham) was only observed in Rln1-/- mice [5].
  • The model of AAD was applied to 12-month-old relaxin-deficient (Rln(-/-)) mice with established airway fibrosis and age-matched wild-type (Rln(+/+)) controls [6].
  • Collectively, the extent of pressure overload-induced LV hypertrophy, fibrosis, and dysfunction were comparable between Rln1+/+ and Rln1-/- mice [7].

High impact information on Rln1

  • Reconstitution of reproductive functions in the ob/ob female necessitates delivery of hypothalamic extracts to the third ventricle (8) and administration of pituitary extract (9), gonadotropic hormones (10), progesterone (11) and relaxin (12) [8].
  • Relaxin has been reported to reduce fibrosis in the kidney, heart, lung, and liver and to promote wound healing [9].
  • Relaxin promotes growth and softening of the cervix, thus facilitating rapid delivery of live young [9].
  • Whereas relaxin is required for development of the mammary nipples in rats and mice, it is essential for prepartum development of glandular parenchyma in pregnant pigs [9].
  • Finally, relaxin counteracts allergic reactions [9].

Chemical compound and disease context of Rln1


Biological context of Rln1


Anatomical context of Rln1

  • We also characterized the temporal expression of the RLX receptor (LGR7) and demonstrated gene transcripts in the myometrium of Rlx+/+ and Rlx-/- mice [14].
  • Endocrine effects of relaxin overexpression in mice [17].
  • The current study examined phenotypic differences in collagen, matrix metalloproteinases (MMP), and estrogen receptors (ERs) in the cervix and vagina of pregnant Rlx+/+ and Rlx-/- mice [4].
  • Ovariectomy of Rln1+/+ mice also led to a significant increase in airway smooth muscle (SM) (lung) thickening, which was further exaggerated in Rln1-/- mice [5].
  • These coherent findings indicate that relaxin regulates fibroblast proliferation, differentiation, and collagen deposition and may have therapeutic potential in diseased states characterized by cardiac fibrosis [18].

Associations of Rln1 with chemical compounds

  • Both genes encode a putative prohormone sequence incorporating the classic two-chain, three cysteine-bonded structure of the relaxin/insulin family and, importantly, contain the RXXXRXX(I/V) motif in the B-chain that is essential for relaxin receptor binding [19].
  • Heterozygous (rlx+/-) mice lactate normally [20].
  • As proliferation and differentiation of uterine and vaginal epithelia are thought to be induced by a paracrine stromal factor that acts upon estrogen stimulation, our results indicate that relaxin may be this paracrine factor [21].
  • Vaginal and cervical luminal epithelia, which proliferated markedly in the rlx +/+ pregnant mice, remained relatively atrophic in the rlx -/- mice [21].
  • Relaxin is a 6 kDa protein hormone produced by the corpus luteum and secreted into the blood during pregnancy in rodents and humans [22].

Regulatory relationships of Rln1


Other interactions of Rln1


Analytical, diagnostic and therapeutic context of Rln1

  • ERT significantly decreased airway fibrosis, airway SM thickening, and cardiac hypertrophy when administered to ovariectomized Rln1-/- mice (all P < 0.05 vs. ovariectomy alone) [5].
  • The expression of this novel relaxin gene was studied in mouse tissues using RT-PCR, where transcripts were identified with a pattern of expression distinct from that of the previously characterized mouse relaxin [19].
  • These data, together with the localization of transcripts in the pars ventromedialis of the dorsal tegmental nucleus of C57BLK6J mouse brain by in situ hybridization histochemistry, suggest a new role for relaxin in neuropeptide signaling processes [19].
  • We have used gene targeting to generate relaxin (rlx)-deficient mice [20].
  • Sequence analysis in combination with mass spectrometry and tryptic peptide mapping showed unambiguously that RLF is larger than previously assumed and that it has the relaxin-type disulfide bond distribution that makes it a bona fide member of the relaxin family of hormones [24].


  1. Relaxin: new peptides, receptors and novel actions. Bathgate, R.A., Samuel, C.S., Burazin, T.C., Gundlach, A.L., Tregear, G.W. Trends Endocrinol. Metab. (2003) [Pubmed]
  2. Genetic targeting of relaxin and insulin-like factor 3 receptors in mice. Kamat, A.A., Feng, S., Bogatcheva, N.V., Truong, A., Bishop, C.E., Agoulnik, A.I. Endocrinology (2004) [Pubmed]
  3. Functional expression of mouse relaxin and mouse relaxin-3 in the lung from an Ebola virus glycoprotein-pseudotyped lentivirus via tracheal delivery. Silvertown, J.D., Walia, J.S., Summerlee, A.J., Medin, J.A. Endocrinology (2006) [Pubmed]
  4. Mechanisms of relaxin action in the reproductive tract: studies in the relaxin-deficient (Rlx-/-) mouse. Parry, L.J., McGuane, J.T., Gehring, H.M., Kostic, I.G., Siebel, A.L. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  5. The effects of relaxin and estrogen deficiency on collagen deposition and hypertrophy of nonreproductive organs. Lekgabe, E.D., Royce, S.G., Hewitson, T.D., Tang, M.L., Zhao, C., Moore, X.L., Tregear, G.W., Bathgate, R.A., Du, X.J., Samuel, C.S. Endocrinology (2006) [Pubmed]
  6. Relaxin plays an important role in the regulation of airway structure and function. Samuel, C.S., Royce, S.G., Burton, M.D., Zhao, C., Tregear, G.W., Tang, M.L. Endocrinology (2007) [Pubmed]
  7. Endogenous relaxin does not affect chronic pressure overload-induced cardiac hypertrophy and fibrosis. Xu, Q., Lekgabe, E.D., Gao, X.M., Ming, Z., Tregear, G.W., Dart, A.M., Bathgate, R.A., Samuel, C.S., Du, X.J. Endocrinology (2008) [Pubmed]
  8. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Chehab, F.F., Lim, M.E., Lu, R. Nat. Genet. (1996) [Pubmed]
  9. Relaxin's physiological roles and other diverse actions. Sherwood, O.D. Endocr. Rev. (2004) [Pubmed]
  10. Relaxin-1-deficient mice develop an age-related progression of renal fibrosis. Samuel, C.S., Zhao, C., Bond, C.P., Hewitson, T.D., Amento, E.P., Summers, R.J. Kidney Int. (2004) [Pubmed]
  11. Relaxin induces an extracellular matrix-degrading phenotype in human lung fibroblasts in vitro and inhibits lung fibrosis in a murine model in vivo. Unemori, E.N., Pickford, L.B., Salles, A.L., Piercy, C.E., Grove, B.H., Erikson, M.E., Amento, E.P. J. Clin. Invest. (1996) [Pubmed]
  12. Relaxin up-regulates the nitric oxide biosynthetic pathway in the mouse uterus: involvement in the inhibition of myometrial contractility. Bani, D., Baccari, M.C., Nistri, S., Calamai, F., Bigazzi, M., Sacchi, T.B. Endocrinology (1999) [Pubmed]
  13. Myocardial relaxin counteracts hypertrophy in hypertensive rats. Dschietzig, T., Bartsch, C., Kinkel, T., Baumann, G., Stangl, K. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  14. Inhibition of oxytocin receptor and estrogen receptor-alpha expression, but not relaxin receptors (LGR7), in the myometrium of late pregnant relaxin gene knockout mice. Siebel, A.L., Gehring, H.M., Reytomas, I.G., Parry, L.J. Endocrinology (2003) [Pubmed]
  15. Oxytocin and estrogen receptor expression in the myometrium of pregnant relaxin-deficient (Rlx-/-) mice. Siebel, A.L., Gehring, H.M., Vodstrcil, L., Parry, L.J. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  16. A novel Leydig cell cDNA-derived protein is a relaxin-like factor. Büllesbach, E.E., Schwabe, C. J. Biol. Chem. (1995) [Pubmed]
  17. Endocrine effects of relaxin overexpression in mice. Feng, S., Bogatcheva, N.V., Kamat, A.A., Truong, A., Agoulnik, A.I. Endocrinology (2006) [Pubmed]
  18. Relaxin modulates cardiac fibroblast proliferation, differentiation, and collagen production and reverses cardiac fibrosis in vivo. Samuel, C.S., Unemori, E.N., Mookerjee, I., Bathgate, R.A., Layfield, S.L., Mak, J., Tregear, G.W., Du, X.J. Endocrinology (2004) [Pubmed]
  19. Human relaxin gene 3 (H3) and the equivalent mouse relaxin (M3) gene. Novel members of the relaxin peptide family. Bathgate, R.A., Samuel, C.S., Burazin, T.C., Layfield, S., Claasz, A.A., Reytomas, I.G., Dawson, N.F., Zhao, C., Bond, C., Summers, R.J., Parry, L.J., Wade, J.D., Tregear, G.W. J. Biol. Chem. (2002) [Pubmed]
  20. Mice without a functional relaxin gene are unable to deliver milk to their pups. Zhao, L., Roche, P.J., Gunnersen, J.M., Hammond, V.E., Tregear, G.W., Wintour, E.M., Beck, F. Endocrinology (1999) [Pubmed]
  21. Collagen studies in late pregnant relaxin null mice. Zhao, L., Samuel, C.S., Tregear, G.W., Beck, F., Wintour, E.M. Biol. Reprod. (2000) [Pubmed]
  22. Evidence for local relaxin ligand-receptor expression and function in arteries. Novak, J., Parry, L.J., Matthews, J.E., Kerchner, L.J., Indovina, K., Hanley-Yanez, K., Doty, K.D., Debrah, D.O., Shroff, S.G., Conrad, K.P. FASEB J. (2006) [Pubmed]
  23. Relaxin favors the morphofunctional integration between skeletal myoblasts and adult cardiomyocytes in coculture. Formigli, L., Francini, F., Chiappini, L., Zecchi-Orlandini, S., Bani, D. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  24. The primary structure and the disulfide links of the bovine relaxin-like factor (RLF). Büllesbach, E.E., Schwabe, C. Biochemistry (2002) [Pubmed]
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