Malformation of stria vascularis in the developing inner ear of the German waltzing guinea pig

Abstract

Auditory function and cochlear morphology have previously been described in the postnatal German waltzing guinea pig, a strain with recessive deafness. In the present study, cochlear histopathology was further investigated in the inner ear of the developing German waltzing guinea pig (gw/gw). The lumen of the cochlear duct diminished progressively from embryonic day (E) 35 to E45 and was absent at E50 because of the complete collapse of Reissner's membrane onto the hearing organ. The embryonic stria vascularis, consisting of a simple epithelium, failed to transform into the complex trilaminar tissue seen in normal animals and displayed signs of degeneration. Subsequent degeneration of the sensory epithelium was observed from E50 and onwards. Defective and insufficient numbers of melanocytes were observed in the developing gw/gw stria vascularis. A gene involved in cochlear melanocyte development, Pax3, was markedly reduced in lateral wall tissue of the cochlea of both E40 and adult gw/gw individuals, whereas its expression was normal in the skin and diaphragm muscle of adult gw/gw animals. The Pax3 gene may thus be involved in the pathological process but is unlikely to be the primary mutated gene in the German waltzing guinea pig. TUNEL assay showed no signs of apoptotic cell death in the developing stria vascularis of this type of guinea pig. Thus, malformation of the stria vascularis appears to be the primary defect in the inner ear of the German waltzing guinea pig. Defective and insufficient numbers of melanocytes might migrate to the developing stria vascularis but fail to provide the proper support for the subsequent development of marginal and basal cells, thereby leading to stria vascularis malformation and dysfunction in the inner ear of the German waltzing guinea pig.

Nkcc1 (Slc12a2) is required for the regulation of endolymph volume in the otic vesicle and swim bladder volume in the zebrafish larva

“…Apical secretion of K + is mediated by channels such as KCNE1 and KCNQ1, with an associated transport of water Vetter et al, 1996); a loss of K + recycling with a concomitant loss of water secretion is thought to lead to a loss of fluid in the scala media, causing Reissner's membrane to collapse (Delpire and Mount, 2002;Wangemann, 2002). NKCC1 is probably involved in maintaining endolymph volume in the guinea pig (Jin et al, 2007); the gw mutant has a similar vestibulocochlear impairment to that in mice mutant for Nkcc1, with a collapse of the endolymphatic compartment and degeneration of many cochlear cell types. Mutant animals show a loss of NKCC1 protein expression in the ear, together with a loss of immunoreactivity for the tight junction protein CLDN11 and the potassium channel KCNJ10 (Jin et al, 2008).…”

Perplexing Pax: From puzzle to paradigm

“…Melanocytes Not specified (Gershon et al, 2005) Mouse Brain Nuclei of pons/medulla, cerebellum Differentiation, maintenance and functional assembly of specific subsets of cells (Stoykova and Gruss, 1994) GWGP Cochlear Melanocytes Formation of melanocytes to support development of marginal and basal cells for correct formation of stria vascularis of the cochlear, function in adult not known (Jin et al, 2007)…”

The morphological and functional development of the stria vascularis in miniature pigs

“…The development of stria vascularis in humans (Lavigne-Rebillard and Bagger-Sjöbäck 1992), mice (Kikuchi and Hilding 1966), rats (Sagara et al 1995), cats (Fernández and Hinojosa 1974), dogs (Coppens et al 2003), rabbits (Grisanti 1957) and guinea pigs (Jin et al 2007) has been examined. Pigs share similarities with humans, especially in terms of the size and shape of the middle and inner ear.…”