Positional cloning of the gene LIMBIN responsible for bovine chondrodysplastic dwarfism.
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.
Takeda
Haruko
H
Shirakawa Institute of Animal Genetics, Nishi-shirakawa, Fukushima 961-8061, Japan.
Takami
Marika
M
Oguni
Tomoko
T
Tsuji
Takehito
T
Yoneda
Kazuhiro
K
Sato
Hiroaki
H
Ihara
Naoya
N
Itoh
Tomohito
T
Kata
Srinivas R
SR
Mishina
Yuji
Y
Womack
James E
JE
Moritomo
Yasuo
Y
Sugimoto
Yoshikazu
Y
Kunieda
Tetsuo
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004392:Dwarfism / Q000235:genetics / Q000662:veterinary*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010009:Osteochondrodysplasias / Q000235:genetics / Q000662:veterinary*; D010375:Pedigree; D011506:Proteins / Q000235:genetics*
D018076:DNA, Complementary; D011506:Proteins