Objective   To examine the expression of tight-junction connexin ZO-1 in the stria vascularis tissue of the cochlea by using spontaneous endolymphatic hydrops animal model constructed with PHEX gene mutant mice, and to analyze the dynamic changes of the gene mutant mice in pathology, imaging, and hearing function.

  Methods   Male Hyp-Duk/Y mice with PHEX gene mutation were selected as the experimental group at three time points, 21 days post birth (P21), 90 days post birth (P90) and 120 days post birth (P120), and wild-type male mice of the same ages were selected as the control groups. The cochlear sections were HE-stained in order to observe whether endolymphatic hydrops was present or absent and to assess its severity. The expression of connexin ZO-1 in both groups was evaluated through immunohistochemical staining of cochlear sections. Auditory-evoked brainstem response (ABR) was induced in both groups at P90 and gadolinium-enhanced MRI was conducted in vivo to observe the middle-order endolymphatic dilatation of cochlea in experimental and control mice aged P21, P90 and P120.

  Results   HE staining of pathological sections of PHEX Hyp-Duk/Y mice aged P90 and P120 showed increased endolymphatic hydronephrosis. The level of striae ZO-1 in PHEX Hyp-Duk/Y mice aged P90 and P120 was significantly lower than that of the controls of the same age (P<0.05). The expression level of ZO-1 was significantly negatively correlated with the degree of endolymphatic hydronephrosis (r=−0.939, P<0.01). The bilateral ABR threshold of PHEX Hyp-Duk/Y mice aged P90 was higher than that of the wild-type mice of the same age, and the mutant mice showed asymmetric hearing loss on both sides. Severe endolymphatic hydronephrosis was observed in PHEX Hyp-Duk/Y mice aged P90 and P120 through in vivo MRI gadolinium imaging.

  Conclusion   PHEX Hyp-Duk/Y can be used as a sound model for basic research of Ménière’s disease. Compared with wild-type mice, PHEX Hyp-Duk/Y mice showed decreased expression of connexin protein ZO-1, which damaged the function of the blood-labyrinth barrier in stria vascularis, and was involved in the formation of endolymphatic hydrops. 7.0 T MRI gadolinium imaging can be used to observe the changes of severe endolymphatic hydrops in mice in vivo, providing imaging basis for the diagnosis of Ménière’s disease.