A Genetic Murine Model of Endolymphatic Hydrops: The Phex Mouse

Abstract

Animal models of endolymphatic hydrops (ELH) provide critical insight into the pathophysiology of Meniere’s disease (MD). A new genetic murine model, called the Phex mouse, circumvents prior need for a time and cost-intensive surgical procedure to create ELH. The Phex mouse model of ELH, which also has X-linked hypophosphatemic rickets, creates a postnatal, spontaneous, and progressive ELH whose phenotype has a predictable decline of vestibular and hearing function reminiscent of human MD. The Phex mouse enables real-time histopathologic analysis to assess diagnostic and therapeutic interventions as well as further our understanding of ELH’s adverse effects. Already the model has validated electrocochleography and cervical vestibular evoked myogenic potential as useful diagnostic tools. New data on caspase activity in apoptosis of the spiral ganglion neurons may help target future therapeutic interventions. This paper highlights the development of the Phex mouse model and highlights its role in characterizing ELH.

Treatment of ear and bone disease in the Phex mouse mutant with dietary supplementation

“…Since 2004, the Phex mouse has served as a valuable model to study the pathophysiology of ELH [7,9,24]. In addition to ELH, the Phex gene mutation causes XLH and its characteristic osteomalacia.…”

“…The development of the Phex mouse model and its otologic manifestations has previously been described [7,9,24]. In brief, XLH is caused by a genetic defect in the Phex gene that leads to a dysfunctional Phex protein.…”

“…The defective Phex protein leads to unmineralized osteoid deposition and soft bone, termed osteomalacia and rickets. Additionally, the impaired Phex-MEPE binding leads to an increase in fibroblast growth factor-23 (FGF-23), which is directly responsible for renal phosphate wasting and decreased 1,25-dihydroxyvitamin D production [24,26,27]. …”

“…Multiple studies have characterized the postnatal development and disease manifestations in the Phex mouse [7,9,23,24,30,31]. At birth, the mice have normal inner ear histology including no ELH, spiral ganglion degeneration, or endolymphatic duct obstruction.…”

Experimental Animal Models for Meniere’s Disease: A Mini-Review

“…Sheykholeslami, et al [35] reported that compared to 10 adult normal mice (P60-P90), the Hyp-Duk/Y mice had either absent or elevated cervical vestibular evoked myogenic potential (cVEMP) with a threshold of a 60 dB normal hearing level. Although the PHEX mutation is not seen in patents of MD, the PHEX murine model (Hyp-Duk/Y) certainly can serve as a viable mouse model that develops typical impaired hearing and balance symptoms for MD [36]. Future studies will enable the PHEX mouse to be a key animal model to hearing research for MD.…”