Grey-lethal mutation induces severe malignant autosomal recessive osteopetrosis in mouse and human - PubMed (original) (raw)

doi: 10.1038/nm842. Epub 2003 Mar 10.

Affiliations

PMID: 12627228
DOI: 10.1038/nm842

Grey-lethal mutation induces severe malignant autosomal recessive osteopetrosis in mouse and human

Nader Chalhoub et al. Nat Med. 2003 Apr.

Abstract

The spontaneous mouse grey-lethal (gl) mutation is responsible for a coat color defect and for the development of the most severe autosomal recessive form of osteopetrosis. Using a positional cloning approach, we have mapped and isolated the gl locus from a approximately 1.5 cM genetic interval. The gl locus was identified in a bacterial artificial chromosome (BAC) contig by functional genetic complementation in transgenic mice. Genomic sequence analysis revealed that the gl mutation is a deletion resulting in complete loss of function. The unique approximately 3 kb wild-type transcript is expressed primarily in osteoclasts and melanocytes as well as in brain, kidney, thymus and spleen. The gl gene is predicted to encode a 338-amino acid type I transmembrane protein that localizes to the intracellular compartment. Mutation in the human GL gene leads to severe recessive osteopetrosis. Our studies show that mouse Gl protein function is absolutely required for osteoclast and melanocyte maturation and function.

PubMed Disclaimer

Comment in

Bad bones, grey hair, one mutation.
Boyce BF. Boyce BF. Nat Med. 2003 Apr;9(4):395-6. doi: 10.1038/nm0403-395. Nat Med. 2003. PMID: 12669057 No abstract available.

Cited by

Molecular biology of bone remodelling.
Rucci N. Rucci N. Clin Cases Miner Bone Metab. 2008 Jan;5(1):49-56. Clin Cases Miner Bone Metab. 2008. PMID: 22460846 Free PMC article.
New knowledge on critical osteoclast formation and activation pathways from study of rare genetic diseases of osteoclasts: focus on the RANK/RANKL axis.
Crockett JC, Mellis DJ, Scott DI, Helfrich MH. Crockett JC, et al. Osteoporos Int. 2011 Jan;22(1):1-20. doi: 10.1007/s00198-010-1272-8. Epub 2010 May 11. Osteoporos Int. 2011. PMID: 20458572 Review.
Lysosomal Storage and Albinism Due to Effects of a De Novo CLCN7 Variant on Lysosomal Acidification.
Nicoli ER, Weston MR, Hackbarth M, Becerril A, Larson A, Zein WM, Baker PR 2nd, Burke JD, Dorward H, Davids M, Huang Y, Adams DR, Zerfas PM, Chen D, Markello TC, Toro C, Wood T, Elliott G, Vu M; Undiagnosed Diseases Network; Zheng W, Garrett LJ, Tifft CJ, Gahl WA, Day-Salvatore DL, Mindell JA, Malicdan MCV. Nicoli ER, et al. Am J Hum Genet. 2019 Jun 6;104(6):1127-1138. doi: 10.1016/j.ajhg.2019.04.008. Epub 2019 May 30. Am J Hum Genet. 2019. PMID: 31155284 Free PMC article.
The virulence gene and clinical phenotypes of osteopetrosis in the Chinese population: six novel mutations of the CLCN7 gene in twelve osteopetrosis families.
Wang C, Zhang H, He JW, Gu JM, Hu WW, Hu YQ, Li M, Liu YJ, Fu WZ, Yue H, Ke YH, Zhang ZL. Wang C, et al. J Bone Miner Metab. 2012 May;30(3):338-48. doi: 10.1007/s00774-011-0319-z. Epub 2011 Sep 28. J Bone Miner Metab. 2012. PMID: 21947783
Targeting strategies for bone diseases: signaling pathways and clinical studies.
Xu H, Wang W, Liu X, Huang W, Zhu C, Xu Y, Yang H, Bai J, Geng D. Xu H, et al. Signal Transduct Target Ther. 2023 May 17;8(1):202. doi: 10.1038/s41392-023-01467-8. Signal Transduct Target Ther. 2023. PMID: 37198232 Free PMC article. Review.

Grey-lethal mutation induces severe malignant autosomal recessive osteopetrosis in mouse and human - PubMed (original) (raw)