Expression of Aquaporin 1 and 5 in the Developing Mouse Inner Ear and Audiovestibular Assessment of an Aqp5 Null Mutant

Abstract

To examine the potential roles of aquaporins 1 and 5 (AQP1 and AQP5, respectively) in inner ear development and function, we defined their spatial and temporal expression patterns in the developing mouse inner ear and examined the morphologic and physiologic effects of loss of Aqp5 function. Standard in situ hybridization (ISH) and immunohistochemical (IHC) assays were used for expression studies with routine morphologic, behavioral, and physiologic assessments of hearing and balance in Aqp5 null mutant mice. AQP1 was first detected at embryonic day 10.5 (E10.5) in the otocyst but eventually localized to specific nonsensory portions of the inner ear and connective tissue cells surrounding the membranous labyrinth. AQP5 displayed specific cochlear expression, first detectable at E15.5 in the nonsensory epithelium and later restricted to the lateral wall of the cochlear duct near the spiral prominence. AQP5 expression continued through postnatal periods with a change of expression domain to the stria vascularis between postnatal day 7 (P7) and P14. By in situ hybridization and immunohistochemical techniques, subtle differences between transcript and protein expression patterns were noted for both AQP1 and 5. Although AQP5 is dynamically expressed in the developing mouse inner ear, adult Aqp5 knockout mice show normal hearing when tested and normal inner ear structural development. These results suggest redundant or alternative mechanisms that likely regulate water homeostasis in the developing and mature inner ear.

Immunohistochemical localization of aquaporins in the human inner ear

“…AQPs 2, 3, 5, 7, 8, 9, and 10). However, previous studies have reported the expression of AQPs in the inner ear of several animal models (Fukushima et al 2004;Huang et al 2002;Merves et al 2003;Zhong and Liu 2003). For example, AQP2 is expressed in the endolymphatic sac of guinea pig and human (Couloigner et al 2004).…”

“…In the inner ear, expression of AQPs 1, 2, 4, and 5 has been reported in the rat, mouse, and guinea pig (Beitz et al 1999(Beitz et al , 2003Huang et al 2002;Li and Verkam 2001;Merves et al 2003;Mhatre et al 1999Mhatre et al , 2002aMiyabe et al 2002;Sawada et al 2002Sawada et al , 2003Stankovic et al 1995;Takumi et al 1998;Zhong and Liu 2003). Dysfunction or lack of AQPs has been described in a variety of diseases, such as nephrogenic diabetes insipidus, early onset of cataract, Sjogren's syndrome, wet lung syndrome, congestive heart failure, and brain edema (for reviews, see Agre et al 2002;Agre and Kozone 2003).…”

“…In the inner ear, the role of AQPs in water homeostasis has been elusive. To date, mutants lacking AQP1, AQP3, AQP4, and AQP5 have been generated (Li and Verkam 2001;Merves et al 2003;Mhatre et al 2002a,b). Surprisingly, all these knockout mice show normal inner ear morphology.…”

Immunohistochemical localization and mRNA expression of aquaporins in the macula utriculi of patients with Meniere’s disease and acoustic neuroma

“…The role of AQP1 that localizes to mesenchymal cells in the animal and human cochlea and vestibule has been proposed to be the transport of water molecules external to the endolymphatic compartment, regulating the osmotic environment adjacent to the scala media (Merves et al 2005; Stankovic et al 1995; Takumi et al 1998). …”

Pendrin Function in Airway Epithelia

“…In bronchial epithelial cells, IL-4 has been shown to alter ion transport by changes in expression; the cytokine decreased expression of the β and γ subunits of ENaC [43], and increased the expression of CFTR [43], CLCA1 and CLCA3 (human equivalent of murine gob-5) [6, 44,45].While the end effect on ion transport (in terms of direction) by IL-4 and IL-13 seems to be tissue-dependent, a common theme emerges; both cytokines alter Na + and Cl -current. In terms of AQP regulation, both the mRNA and protein levels of two AQP isoforms are regulated by IL-13 in the lung; AQP3 is increased whereas AQP5 is decreased [46]. Interestingly, decreased expression of this water channel isoform has been associated with increased mucus production [47,48].…”