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Lrp5  -  low density lipoprotein receptor-related...

Mus musculus

Synonyms: BMND1, HBM, LR3, LRP-5, LRP-7, ...
 
 
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Disease relevance of Lrp5

 

High impact information on Lrp5

 

Biological context of Lrp5

  • One of these sites within the Lrp5 locus was discovered to confer vitamin D response to a heterologous promoter when introduced into osteoblastic cells, permitting both the identification and characterization of the vitamin D response element located within [4].
  • Interestingly, additional studies revealed that whereas the regulatory region in the mouse Lrp5 gene was highly conserved in the human genome, the vitamin D response element was not [4].
  • RESULTS: Mice heterozygous for mutations in Lrp6 and either heterozygous or homozygous for a mutation in Lrp5 (Lrp6(+/-);Lrp5(+/-) or Lrp6(+/-);Lrp5(-/-)) display limb defects with incomplete penetrance and variable expression [5].
  • The canonical pathway of Wnt signaling has been implicated by studies of Lrp5, a co-receptor for Wnt proteins, in postnatal bone mass homeostasis [6].
  • Lrp5-null (Lrp5-/-) mice exhibited significantly lower bone mineral density and decreased strength [7].
 

Associations of Lrp5 with chemical compounds

  • We gavage-fed lithium chloride to 8-week-old mice from three different strains (Lrp5(-/-), SAMP6, and C57BL/6) and assessed the effect on bone metabolism after 4 weeks of therapy [3].
  • The high bone mass (HBM) mutation was identified as a glycine to valine substitution at amino acid residue 171 in the gene coding for low-density lipoprotein receptor-related protein 5 (LRP5) [Bone Miner. Res. 16(4) (2001) 758] [8].
 

Physical interactions of Lrp5

  • The Dkk family of secreted cysteine-rich proteins regulates Wnt/beta-catenin signaling by interacting with the Wnt co-receptor Lrp5/6 [9].
 

Other interactions of Lrp5

 

Analytical, diagnostic and therapeutic context of Lrp5

  • 4. The LRP7 gene was also localized by radiation hybrid mapping between markers D11S24270 and D11S1975 [13].
  • Acupuncture was then applied to acupoints Yanglingquan (GB34) and Taichong (LR3) starting 2 h after the first MPTP administration and then at 48 h intervals until the mice were sacrificed for analyses at 1, 3, and 7 days after the last MPTP injection [14].

References

  1. Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. Kato, M., Patel, M.S., Levasseur, R., Lobov, I., Chang, B.H., Glass, D.A., Hartmann, C., Li, L., Hwang, T.H., Brayton, C.F., Lang, R.A., Karsenty, G., Chan, L. J. Cell Biol. (2002) [Pubmed]
  2. Severe hypercholesterolemia, impaired fat tolerance, and advanced atherosclerosis in mice lacking both low density lipoprotein receptor-related protein 5 and apolipoprotein E. Magoori, K., Kang, M.J., Ito, M.R., Kakuuchi, H., Ioka, R.X., Kamataki, A., Kim, D.H., Asaba, H., Iwasaki, S., Takei, Y.A., Sasaki, M., Usui, S., Okazaki, M., Takahashi, S., Ono, M., Nose, M., Sakai, J., Fujino, T., Yamamoto, T.T. J. Biol. Chem. (2003) [Pubmed]
  3. Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice. Clément-Lacroix, P., Ai, M., Morvan, F., Roman-Roman, S., Vayssière, B., Belleville, C., Estrera, K., Warman, M.L., Baron, R., Rawadi, G. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  4. 1,25-Dihydroxyvitamin D3 regulates the expression of low-density lipoprotein receptor-related protein 5 via deoxyribonucleic acid sequence elements located downstream of the start site of transcription. Fretz, J.A., Zella, L.A., Kim, S., Shevde, N.K., Pike, J.W. Mol. Endocrinol. (2006) [Pubmed]
  5. Decreased BMD and limb deformities in mice carrying mutations in both Lrp5 and Lrp6. Holmen, S.L., Giambernardi, T.A., Zylstra, C.R., Buckner-Berghuis, B.D., Resau, J.H., Hess, J.F., Glatt, V., Bouxsein, M.L., Ai, M., Warman, M.L., Williams, B.O. J. Bone Miner. Res. (2004) [Pubmed]
  6. Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Hu, H., Hilton, M.J., Tu, X., Yu, K., Ornitz, D.M., Long, F. Development (2005) [Pubmed]
  7. The Wnt co-receptor LRP5 is essential for skeletal mechanotransduction but not for the anabolic bone response to parathyroid hormone treatment. Sawakami, K., Robling, A.G., Ai, M., Pitner, N.D., Liu, D., Warden, S.J., Li, J., Maye, P., Rowe, D.W., Duncan, R.L., Warman, M.L., Turner, C.H. J. Biol. Chem. (2006) [Pubmed]
  8. Bone biomechanical properties in LRP5 mutant mice. Akhter, M.P., Wells, D.J., Short, S.J., Cullen, D.M., Johnson, M.L., Haynatzki, G.R., Babij, P., Allen, K.M., Yaworsky, P.J., Bex, F., Recker, R.R. Bone (2004) [Pubmed]
  9. Dkk2 plays an essential role in the corneal fate of the ocular surface epithelium. Mukhopadhyay, M., Gorivodsky, M., Shtrom, S., Grinberg, A., Niehrs, C., Morasso, M.I., Westphal, H. Development (2006) [Pubmed]
  10. The Wnt co-receptors Lrp5 and Lrp6 are essential for gastrulation in mice. Kelly, O.G., Pinson, K.I., Skarnes, W.C. Development (2004) [Pubmed]
  11. Hypomorphic expression of Dkk1 in the doubleridge mouse: dose dependence and compensatory interactions with Lrp6. MacDonald, B.T., Adamska, M., Meisler, M.H. Development (2004) [Pubmed]
  12. Interaction between LRP5 and Frat1 mediates the activation of the Wnt canonical pathway. Hay, E., Faucheu, C., Suc-Royer, I., Touitou, R., Stiot, V., Vayssière, B., Baron, R., Roman-Roman, S., Rawadi, G. J. Biol. Chem. (2005) [Pubmed]
  13. Molecular cloning of mouse Lrp7(Lr3) cDNA and chromosomal mapping of orthologous genes in mouse and human. Chen, D., Lathrop, W., Dong, Y. Genomics (1999) [Pubmed]
  14. Acupuncture inhibits microglial activation and inflammatory events in the MPTP-induced mouse model. Kang, J.M., Park, H.J., Choi, Y.G., Choe, I.H., Park, J.H., Kim, Y.S., Lim, S. Brain Res. (2007) [Pubmed]
 
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