Positional cloning of the gene LIMBIN responsible for bovine chondrodysplastic dwarfism. Academic Article uri icon

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 approximately 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.

published proceedings

  • Proc Natl Acad Sci U S A

altmetric score

  • 3

author list (cited authors)

  • Takeda, H., Takami, M., Oguni, T., Tsuji, T., Yoneda, K., Sato, H., ... Kunieda, T.

citation count

  • 63

complete list of authors

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

publication date

  • August 2002