Genetic modification of the inner ear lateral semicircular canal phenotype of the Bmp4 haplo-insufficient mouse.
In the mouse, development of the lateral semicircular canal of the inner ear is sensitive to Bmp4 heterozygosity. In the C57BL6 background 30% of the heterozygotes display circling behavior, 66% have a specific defect in the vestibular part of the inner ear, namely the constriction, interruption or absence of the lateral semicircular canal. Only mice having both ears affected display circling behavior. In the (C57BL6xCBA)N1 background, the penetrance of the canal phenotype is greatly reduced, and bilateral lateral canal defect is not sufficient to induce circling. We found association of the canal phenotype with the genotype of markers on chromosome 14 and 4, co-localizing with Ecs and Eclb identified in the Ecl mouse with similar lateral canal defects. Candidate genes to contain the causal mutation are Bmp4 on chromosome 14, and Rere on chromosome 4.
Vervoort
Raf
R
Laboratory of Glycobiology and Developmental Genetics, Flanders Institute for Biotechnology (VIB) and Department of Human Genetics, Katholieke Universiteit Leuven, Herestraat 49 bus 602, B-3000 Leuven, Belgium. ribvervoort@hotmail.com
Ceulemans
Helga
H
Van Aerschot
Leen
L
D'Hooge
Rudi
R
David
Guido
G
D000818:Animals; D001522:Behavior, Animal; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics*; D007758:Ear, Inner / Q000002:abnormalities; D006239:Haplotypes; D006579:Heterozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D012665:Semicircular Canals / Q000002:abnormalities*
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4