Morphological observation of the stria vascularis in midkine and pleiotrophin knockout mice.
OBJECTIVE
Midkine and Pleiotrophin are low molecular weight basic proteins with closely related structures and serve as growth/differentiation factors. They have been reported to be expressed in the cochlea during the embryonic and perinatal periods. In the present study, we focused on the roles of midkine and pleiotrophin in the stria vascularis and investigated morphological changes using mice deficient in these genes.


METHODS
Midkine knockout, pleiotrophin knockout, and double knockout mice were used and compared to wild-type mice. Auditory brain stem responses (ABRs) and cochlear blood flows were measured in each type of mice. Pathological changes in the stria vascularis were examined by light microscopy, including immunohistochemical staining with anti-Kir4.1 antibody, and electron microscopy.


RESULTS
Hearing thresholds examined by ABRs were significantly higher in midkine knockout and pleiotrophin knockout mice than in wild-type mice. Double knockout mice showed higher thresholds compared to midkine knockout and pleiotrophin knockout mice. Blood flow in the lateral walls did not significantly differ and light microscopy examination showed an almost normal appearance of the stria vascularis in these knockout mice. However, the expression of Kir4.1 was weak in the knockout mice and severe vacuolar degeneration was observed by electron microscopy in the intermediate cells of the double knockout mice.


CONCLUSIONS
The present study demonstrates that midkine and pleiotrophin play some roles for the morphological maintenance of intermediate cell in the stria vascularis.
Sone
Michihiko
M
Department of Otolaryngology, Nagoya University Graduate School of Medicine, Japan. michsone@med.nagoya-u.ac.jp
Muramatsu
Hisako
H
Muramatsu
Takashi
T
Nakashima
Tsutomu
T
D000818:Animals; D000906:Antibodies; D001309:Auditory Threshold / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology*; D003051:Cochlea / Q000098:blood supply; D016207:Cytokines / Q000502:physiology*; D016057:Evoked Potentials, Auditory, Brain Stem; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D000078792:Midkine; D024661:Potassium Channels, Inwardly Rectifying / Q000032:analysis; D013316:Stria Vascularis / Q000473:pathology*; D000098854:Kcnj10 Channel
D000906:Antibodies; D002352:Carrier Proteins; D016207:Cytokines; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; C066845:pleiotrophin; D000078792:Midkine