The role of bone morphogenetic protein 4 in inner ear development and function.
Bone Morphogenetic Protein 4 (BMP4) is a member of the TGF-beta superfamily and is known to be important for the normal development of many tissues and organs, including the inner ear. Bmp4 homozygous null mice die as embryos, but Bmp4 heterozygous null (Bmp4(+/-)) mice are viable and some adults exhibit a circling phenotype, suggestive of an inner ear defect. To understand the role of BMP4 in inner ear development and function, we have begun to study C57BL/6 Bmp4(+/-) mice. Quantitative testing of the vestibulo-collic reflex, which helps maintain head stability, demonstrated that Bmp4(+/-) mice that exhibit circling behavior have a poor response in the yaw axis, consistent with semicircular canal dysfunction. Although the hair cells of the ampullae were grossly normal, the stereocilia were greatly reduced in number. Auditory brainstem responses showed that Bmp4(+/-) mice have elevated hearing thresholds and immunohistochemical staining demonstrated decreased numbers of neuronal processes in the organ of Corti. Thus Bmp4(+/-) mice have structural and functional deficits in the inner ear.
Blauwkamp
Marsha N
MN
Cellular and Molecular Biology Program, 2966 Taubman Medical Library, University of Michigan, Ann Arbor, MI 48109-0619, USA. mousman@med.umich.edu
Beyer
Lisa A
LA
Kabara
Lisa
L
Takemura
Keiji
K
Buck
Timothy
T
King
W M
WM
Dolan
David F
DF
Barald
Kate F
KF
Raphael
Yehoash
Y
Koenig
Ronald J
RJ
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001522:Behavior, Animal; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003051:Cochlea / Q000473:pathology; D007758:Ear, Inner / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D016057:Evoked Potentials, Auditory, Brain Stem; D015870:Gene Expression; D006198:Hair Cells, Auditory / Q000473:pathology; D034381:Hearing Loss / Q000235:genetics / Q000503:physiopathology; D006579:Heterozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics; D010641:Phenotype; D012018:Reflex / Q000502:physiology; D012665:Semicircular Canals / Q000503:physiopathology
D051792:Basic Helix-Loop-Helix Proteins; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D009419:Nerve Tissue Proteins; C525810:Bmp4 protein, mouse; C486336:Neurog1 protein, mouse