Positional cloning of the gene LIMBIN responsible for bovine chondrodysplastic dwarfism

Haruko Takeda, Marika Takami, Tomoko Oguni, Takehito Tsuji, Kazuhiro Yoneda, Hiroaki Sato, Naoya Ihara, Tomohito Itoh, Srinivas R. Kata, Yuji Mishina, James E. Womack, Yasuo Moritomo, Yoshikazu Sugimoto, Tetsuo Kunieda

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Abstract

Chondrodysplastic dwarfism in Japanese brown cattle is an autosomal recessive disorder characterized by short limbs. Previously, we mapped the locus responsible for the disease on the distal end of bovine chromosome 6. Here, we narrowed the critical region to ≈2 cM by using linkage analysis, constructed a BAC and YAC contig covering this region, and identified a gene, LIMBIN (LBN), that possessed disease-specific mutations in the affected calves. One mutation was a single nucleotide substitution leading to an activation of a cryptic splicing donor site and the other was a one-base deletion resulting in a frameshift mutation. Strong expression of the Lbn gene was observed in limb buds of developing mouse embryos and in proliferating chondrocytes and bone-forming osteoblasts in long bones. These findings indicate that LBN is responsible for bovine chondrodysplastic dwarfism and has a critical role in a skeletal development.

Original languageEnglish
Pages (from-to)10549-10554
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number16
DOIs
Publication statusPublished - Aug 2002

ASJC Scopus subject areas

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    Takeda, H., Takami, M., Oguni, T., Tsuji, T., Yoneda, K., Sato, H., Ihara, N., Itoh, T., Kata, S. R., Mishina, Y., Womack, J. E., Moritomo, Y., Sugimoto, Y., & Kunieda, T. (2002). Positional cloning of the gene LIMBIN responsible for bovine chondrodysplastic dwarfism. Proceedings of the National Academy of Sciences of the United States of America, 99(16), 10549-10554. https://doi.org/10.1073/pnas.152337899