Studies On Mouse Scleraxis Expression In The Ear And Inner Ear Cell Lineage

Scleraxis is a basic helix-loop-helix transcription factor expressed in tendon andligament progenitor cells and the differentiated cells within these connective tissues inthe axial and appendicular skeleton. Unexpectedly, we found expression of the SCXtransgenic reporter mouse, SCX-GFP, in interdental cells, sensory hair cells, andcochlear supporting cells at E18.5. We evaluated SCX-null mice to gain insight intothe function of SCX in the inner ear. Paradoxical hearing loss was detected inSCX-nulls, with~50%of the mutants presenting elevated auditory thresholds.However, SCX-null mice have no obvious, gross alterations in cochlear morphologyor cellular patterning. Moreover, we show that the elevated auditory thresholdscorrelate with middle ear infection. The vertebrate middle ear transmits vibrations ofthe tympanic membrane to the cochlea. The tensor tympani and stapedius musclesinsert into the malleus and stapes via distinct tendons and mediate the middle earmuscle reflex that in part protects the inner ear from noise-induced damage. Nothing,however, is known about the development and function of these tendons. SCX isexpressed in tendon progenitors at E14.5and differentiated tenocytesThe mammalian inner ear subserves the special senses of hearing and balance.The auditory and vestibular sensory epithelia consist of mechanically sensitive haircells and associated supporting cells. Hearing loss and balance dysfunction are mostfrequently caused by compromise of hair cells and/or their innervating neurons. Thedevelopment of gene-and cell-based therapeutics will benefit from a thoroughunderstanding of the molecular basis of patterning and cell fate specification in themammalian inner ear. The goal of this study was to conduct retroviral lineageanalysis of the E11.5mouse otic vesicle. A replication-defective retrovirus encodingPLAP and a variable24-bp oligonucleotide tag was microinjected into the E11.5mouse otocyst. PLAP-positive cells were microdissected from cryostat sections of thepostnatal inner ear and subjected to nested PCR. PLAP-positive cells sharing the same sequence tag were assumed to have arisen from a common progenitor and are clonallyrelated. Thirty five multicellular clones consisting of an average of3.4cells per clonewere identified in the auditory and vestibular sensory epithelia, ganglia, spiral limbus,and stria vascularis. Vestibular hair cells in the posterior crista were related to oneanother, their supporting cells, and nonsensory epithelial cells lining the ampulla. Inthe organ of Corti, outer hair cells were related to a supporting cell type and weretightly clustered. By contrast, spiral ganglion neurons, interdental cells, and Claudius’cells were related to cells of the same type and could be dispersed over hundreds ofmicrons. These data contribute new information about the developmental potential ofmammalian otic precursors in vivo.Ketamine combined with medetomidine (MK) or dexmedetomidine (DK) iswidely used to provide general anaesthesia in laboratory animals. This study aimed toassess the effects of MK or DK treatment on embryogenesis and inner eardevelopment.25pregnant mice were divided into5groups and administratedintraperitoneal (IP) or subcutaneous (SC) with MK or DK at embryonic day8.5. Afterbirth, the pups were counted and weighed at postnatal day0,15and30. For earfunction, brainstem response testing (ABR) was applied to check cochlea; reachingreflex and swimming tests were applied to assess vestibular function. The resultsshowed there was no apparent difference between MK or DK administered either IPor SC in pregnant mouse. No significant differences was found between treatedgroups and control in embryo development and ear function. About10pups werefound in each litter. All the pups could gain normal weight with growth. The ABRthresholds of treated groups are also not statistically significantly different fromcontrol group (P>0.05). And treated pups were able to exhibit normal reaching reflexand swimming behavior, and show normal morphology in all six inner ear sensoryregions. In conclusion, this study did not find ketamine combined with medetomidineor dexmedetomidine had any effect on general embryogenesis and ear function ofmouse offsprings.