Relationship between tinnitus and olfactory dysfunction: audiovisual, olfactory, and medical examinations.

Introduction: Sensory dysfunctions and cognitive impairments are related to each other. Although a relationship between tinnitus and subjective olfactory dysfunction has been reported, there have been no reports investigating the relationship between tinnitus and olfactory test results. Methods: To investigate the relationship between tinnitus and olfactory test results, we conducted sensory tests, including hearing and visual examinations. The subjects included 510 community-dwelling individuals (295 women and 215 men) who attended a health checkup in Yakumo, Japan. The age of the subjects ranged from 40 to 91 years (mean ± standard deviation, 63.8 ± 9.9 years). The participants completed a self-reported questionnaire on subjective tinnitus, olfactory function, and hearing function, as well as their lifestyle. The health checkup included smell, hearing, vision, and blood examinations. Results: After adjusting for age and sex, the presence of tinnitus was significantly associated with subjective olfactory dysfunction, poor olfactory test results, hearing deterioration, vertigo, and headache. Additionally, high serum calcium levels and a low albumin/globulin ratio were significantly associated with low physical activity and nutrition. Women scored higher than men in olfactory and hearing examinations, but there was no gender difference in vision examinations. Conclusion: Subjective smell dysfunction and poor smell test results were significantly associated with tinnitus complaints. Hearing and vision were associated even after adjusting for age and sex. These findings suggest that evaluating the mutual relationships among sensory organs is important when evaluating the influence of sensory dysfunctions on cognitive function.

Relationship between cognitive domains and hearing ability in memory clinic patients: How did the relationship change after 6 months of introducing a hearing aid?

OBJECTIVE: We aimed to evaluate the relationship between hearing ability and cognitive domains and determine how the relationship changes after 6 months of introducing a hearing aid. METHODS: We conducted a 6-month hearing aid lending study between September 2014 and March 2019, including 59 older participants who visited the Memory Clinic at the National Center for Geriatrics and Gerontology. The hearing level was assessed using pure tone audiometry. Speech intelligibility was measured using the monosyllabic word discrimination score. We assessed the relationship between hearing ability and cognitive domains using the Mini-Mental State Examination (MMSE) total score and four subscale scores (orientation, memory, attention, and language). Differences in the cognitive function between baseline (pre-) and 6 months later (post-) after introducing a hearing aid were also assessed. RESULTS: The pre-orientation score was significantly associated with the pure-tone average (p = 0.013), and the pre-language score was significantly associated with speech intelligibility (p = 0.006) after adjusting for confounders. None of the MMSE subscale scores were significantly different between pre- and post-scores, however, an expectation of improvement with continuous hearing aid use was implied in the attention domain. CONCLUSION: We found a significant association between hearing ability and cognitive domains in individuals whose cognitive functions were not considered healthy. The presence of a potential relationship between cognitive domains, hearing ability, and auditory compensation is suggested.

Cognitive impairment is correlated with olfactory identification deficits in older Japanese adults: A cross-sectional study using objective and subjective olfactory measures.

AIM: Olfactory impairment is associated with cognitive impairment. However, differences between subjective and objective olfactory impairment measurements in older adults and their relationship with cognitive impairment are unclear. METHODS: We assessed the relationship between cognitive and olfactory impairments via a single-center observational study in 2020. Forty-seven individuals who visited our memory clinic were enrolled and asked to complete objective and subjective olfactory tests. Participants had dementia, mild cognitive impairment, or normal cognition. We administered the Open Essence (a simple card-type odor identification test) and self-administered odor questionnaire to assess objective and subjective olfaction, respectively, and the Mini-Mental State Examination to assess cognitive function. RESULTS: Older age was related to decreased Open Essence scores (P < 0.001). Compared with the mild cognitive impairment and normal cognition groups, the dementia group had significantly lower Open Essence scores (P < 0.001). Cognitive impairment was also associated with decreased Open Essence scores after adjusting for age, sex, and education (P < 0.001). Participants with dementia did not obtain lower self-administered odor questionnaire scores than those with normal cognition, and they tended to be unaware of their olfactory impairment. CONCLUSION: Open Essence scores significantly decreased according to the degree of cognitive impairment. Participants with dementia were unaware of their olfactory impairment, as indicated by odor questionnaire scores. Objective and subjective scores of olfaction differed in participants with dementia. Concomitant assessment of objective and subjective olfaction is useful to screen older adults with both olfactory and cognitive impairments. Geriatr Gerontol Int 2022; 22: 924-929.

Prevalence of usage of hearing aids and its association with cognitive impairment in Japanese community-dwelling elders with hearing loss.

OBJECTIVE: Hearing loss is a risk factor for cognitive impairment, and the use of a hearing aid (HA) may prevent cognitive decline alongside hearing loss. We aimed to elucidate the prevalence of self-reported HA usage in Japanese community-dwelling elders with hearing loss, and the effect of hearing and HA on cognitive impairment. METHODS: A total of 1193 participants, who had audiometric defined hearing loss and were aged 60 years or over, had their cumulative 3260 observations followed up for 10 years from a large cohort of a Japanese study. Association between hearing (pure-tone average threshold level at 500, 1000, 2000, and 4000 Hz from the better hearing ear: PTABHE) and HA usage with cognitive impairment (total score of Mini-Mental State Estimation was under 27 or diagnosed as dementia) was analyzed using generalized estimating equations. RESULTS: The HA usage rate of the 1193 community-dwelling elders with hearing loss was 6% during the first involvement. The majority (59.2%) of HA users always used an HA. HA usage rate was 0.7% for the mild hearing loss group and 32.4% for the moderate or greater hearing loss group in the latest participating wave. PTABHE was significantly associated with cognitive impairment (odds ratio for every 10 dB 1.36; 95% CI 1.21-1.53, p<0.0001) after adjusting for age, sex, education, depressed mood, smoking status, alcohol intake, income, activity, obesity, histories of hypertension, dyslipidemia, ischemic heart disease, diabetes, stroke, ear disease, and occupational noise exposure. PTABHE was also significantly associated with cognitive impairment in the mild hearing loss group (odds ratio for every 10 dB 1.34; 95% CI 1.05-1.72, p = 0.020) and moderate hearing loss group (odds ratio for every 10 dB 1.82; 95% CI 1.27-2.61, p = 0.001). HA use showed a significant suppressive effect on cognitive impairment in those with moderate hearing loss who always use an HA (odds ratio 0.54; 95% CI 0.30-1.00, p = 0.049). CONCLUSION: The prevalence of HA usage among Japanese community-dwelling elders with hearing loss is consistent, at around 10%. The hearing level remained a primary risk factor for cognitive impairment among elders with hearing loss after adjusting for several confounding factors. Regular HA use may have a protective effect on cognitive impairment in those with moderate hearing loss.

Longitudinal associations between hearing aid usage and cognition in community-dwelling Japanese older adults with moderate hearing loss.

We investigated the associations between hearing aids (HA) and the maintenance of cognitive function among community-dwelling older adults with moderate hearing loss. A total of 407 participants aged 60 years or older with moderate hearing loss were recruited from the National Institute for Longevity Sciences, Longitudinal Study for Aging (NILS-LSA). Moderate hearing loss was defined as a pure-tone average of 40-69 dB at 500, 1000, 2000, and 4000 Hz of the better ear, according to the definition proposed by the Japan Audiological Society. Cognitive function was evaluated using the four subtests of the Japanese version of the Wechsler Adult Intelligence Scale-Revised Short Forms (WAIS-R-SF): Information, Similarities, Picture completion, and Digit Symbol Substitution (DSST). A longitudinal analysis of 1192 observations with a mean follow-up period of 4.5 ± 3.9 years was performed. The HA use rate at any time during the follow-up period was 31.4%, and HA users were significantly younger (t-test, p = 0.001), had worse hearing (p < .0001) and higher education (p = 0.001), participated more frequently in the survey (p < .0001), and were less depressed (χ2 test, p = 0.003) than the older adults not using HA. General linear mixed models consisted of the fixed effects of HA use, follow-up time, and an HA use × time interaction term adjusted for age and pure-tone average thresholds at baseline, sex, education, and other possible confounders. HA use showed significant main effects on the scores for Picture completion and DSST after adjustment; scores were better in the HA use group than in the no HA use group. The HA use × time interaction was significant for the Information score (p = 0.040). The model-predicted 12-year slope with centralizing age indicated that the no HA use group showed greater decline over time on Information scores than did HA use group. The slopes did not differ between HA users and non-users for the Similarities, Picture completion and DSST. In conclusion, HA use may have a protective effect on the decline in general knowledge in older adults with moderate hearing loss.

Effects of endolymphatic hydrops on acoustic energy absorbance.

Background: The presence of endolymphatic hydrops (EH) may cause hearing loss and affect the transmission of acoustic energy to the inner ear.Objectives: Acoustic energy absorbance on wideband acoustic immittance (WAI) was evaluated, focusing especially on EH in the vestibule.Material and methods: A total of 32 ears from 16 patients who underwent 3-T magnetic resonance imaging (MRI) to evaluate the presence of EH were examined, retrospectively. The degree of EH in the vestibule was classified into three grades (no, mild, and significant), and pure tone audiometry (PTA) and WAI were measured before and after a glycerol drip.Results: Ears with significant EH showed significantly higher hearing levels and air-bone gaps (ABG), and higher absorbance values on WAI at low frequencies (560-600 Hz) than ears with mild or no EH. Changes in absorbance values were observed in some ears without threshold change on PTA.Conclusions and Significance: This study showed significantly higher absorbance values of acoustic energy with significant vestibular EH at low frequencies. Considering ABGs observed in ears with significant EH, the presence of EH in the vestibule might cause an obstacle to the transmission of acoustic energy to the inner ear.

Clinical Features of Ears With Otosclerosis and Endolymphatic Hydrops.

OBJECTIVE: Endolymphatic hydrops (EH) has been reported in ears with otosclerosis. The objective of this study was to investigate the clinical features of ears with otosclerosis and EH on magnetic resonance imaging (MRI) and identify predictors for the presence of EH. STUDY DESIGN: Retrospective study. SETTING: University hospital. MATERIALS AND METHODS: Forty-six ears from 37 patients with otosclerosis were included in the present study. INTERVENTIONS: The subjects were divided into three groups, those with no, mild, or significant EH, based on 3-T MRI with intravenous injection of gadolinium. Hearing levels and the extent of otosclerotic lesions graded based on the computed tomography (CT) findings were compared among the groups. Moreover, to examine the vascular activity of the disease, intraoperative measurements of blood flow were also evaluated. MAIN OUTCOME MEASURES: Imaging, hearing levels, and blood flow values. RESULTS: The overall rate of EH was 58.7% (27 of 46 ears); cochlear EH (52.2%) was more frequent than vestibular EH (26.1%). Average thresholds in ears with significant EH were significantly higher at several frequencies, both on air and bone conduction, than those with no or mild EH. Significant EH was more frequently observed in ears with advanced stages on CT than in those without advanced stages. The values of blood flow in the area anterior to the oval window were higher in some ears with EH than in ears without EH. CONCLUSION: EH was frequently present in ears with otosclerosis, especially those with severe hearing loss or advanced disease on CT.

Significance of Endolymphatic Hydrops Herniation Into the Semicircular Canals Detected on MRI.

OBJECTIVE: The objective of this study was to investigate the relationship between endolymphatic hydrops (EH) and hearing level or vestibular symptoms by focusing on EH herniation into the semicircular canal (SCC). STUDY DESIGN: Retrospective study. SETTING: University hospital. METHODS: The study included 1,548 ears of 775 patients who underwent magnetic resonance imaging (MRI) examination in our university hospital to investigate possible EH. MRI was performed 4 hours after intravenous injection of a standard dose of gadodiamide hydrate and/or 24 hours after intratympanic injection of gadopentetate dimeglumine diluted eightfold. The hearing threshold and vestibular symptoms were compared between ears with unilateral and bilateral EH herniation into the SCC and between ears having vestibular EH adjacent to the stapes footplate with or without EH herniation. RESULTS: Forty-four ears (19 men and 25 women, mean age 53.6 yr) showed EH herniation into the SCC. The average hearing thresholds at 500 to 4000 Hz and presence of vestibular EH adjacent to the stapes footplate were significantly higher in ears with unilateral herniation than in those with bilateral herniation. The average hearing thresholds at 500 and 1000 Hz were significantly higher in the group of ears having adjacency with herniation than in those without herniation. Vestibular symptoms did not differ significantly between groups. CONCLUSION: Unilateral herniation occurs with EH progression. Bilateral herniation may occur regardless of EH progression and might be influenced by other factors that alter the membranous labyrinth.

＜Editors' Choice＞ Maxillary sinus carcinoma outcomes over 60 years: experience at a single institution.

Advances in the diagnosis and treatment of patients with maxillary sinus carcinoma have improved patient prognosis. This study investigated changes in demographic and clinical characteristics, treatment methods, and outcomes of patients with maxillary sinus carcinomas during three different 10-year periods spanning 60 years at our university hospital. Of the 233 patients with maxillary sinus carcinomas managed at Nagoya University Hospital, 135 were treated between 1951 and 1960 (first period), 35 between 1981 and 1990 (second period), and 63 between 2003 and 2012 (third period). Patient age, sex, TN classifications, treatment methods, and survival rates were compared among patients treated during these time periods. Of the 135, 35, and 63 patients with maxillary sinus carcinomas treated during these time periods, 86 (63.7%), 21 (51.4%), and 48 (76.2%), respectively, were men; 14 (10.4%), six (17.1%), and 14 (22.2%), respectively, were aged ≥70 years; and 135 (100%), 28 (80.0%), and 43 (68.3%), respectively, were treated surgically. The 5-year overall survival rates in patients treated during the first, second, and third periods were 29.7%, 44.3%, and 57.5%, respectively. These findings indicated that advances in the diagnosis and treatment of patients with maxillary sinus carcinoma, including computed tomography and craniofacial resection, have contributed to improvements in patient survival rates.

Significance of internal auditory canal diverticula in ears with otosclerosis.

BACKGROUND: Diverticula in the internal auditory canal (IAC) have been reported in ears with otosclerosis. OBJECTIVE: We evaluated hearing levels and vascular activity in ears with otosclerosis with and without IAC diverticula and clarify the significance of IAC diverticula. MATERIALS AND METHODS: Sixty-one ears from 54 patients who underwent stapes surgery for otosclerosis [fenestral (48 ears) and retrofenestral (13 ears) groups] were included in the present study. Preoperative hearing levels on pure tone audiometry (PTA) and intraoperative measurements of blood flow were compared between the groups. RESULTS: A total of 24 of 61 ears (39.3%) showed IAC diverticula, significantly higher than the frequency in ears without otosclerosis (3.7%). No significant differences in air- and bone-conduction thresholds on PTA were evident between ears with and without IAC diverticula in each group. Ears without IAC diverticula tended to show higher blood flow in the area anterior to the oval window than ears with IAC diverticula, but the difference was not significant. CONCLUSIONS: The incidence of the IAC diverticula in otosclerosis was significantly higher than in cases without otosclerosis. The existence of IAC diverticula was not evidently related to the severity of the disease from the perspective of hearing level and vascular activity.

Computed tomographic assessment of autologous fat injection augmentation for vocal fold paralysis.

Objective: To perform a quantitative computed tomography (CT) assessment of short- and long-term outcomes of autologous fat injection augmentation in patients with unilateral vocal fold paralysis. Study Design: Retrospective case series. Methods: Twelve patients who had undergone autologous fat injection augmentation for unilateral vocal fold paralysis in our hospital between 2011 and 2015 were enrolled in this study. The autologous fat for injection was acquired from periumbilical subcutaneous tissue and was injected orally using a special-purpose laryngeal injection needle. To evaluate the injected fat at the follow-up assessments, CT was performed at several times after surgery in clinical practice. All thin-section CT images were transferred to a workstation, and the volume of the injected fat was calculated. Results: Patients comprised 6 men and 6 women with a mean age at the time of surgery of 62.9 years (range, 46-82 years). The actual injected fat volume was 1.1-2.5 ml (mean, 1.6 ml). In seven patients assessed by CT two days after surgery, the average residual rate of the injected fat was 63.9%. The mean residual rates of the injected fat were 30.0% at 3 months, 33.7% at 6 months, 29.2% at 12 months, and 32.0% at 24 months. Conclusions: Although the injected fat volume decreased within the first three months and the residual rate of the injected fat was 30.0% at three months after injection, the residual fat volume remained at the same level for 24 months after injection. Level of Evidence: 4.

Idiopathic sudden sensorineural hearing loss in Japan.

CONCLUSION: An epidemiological survey of hospitals and private clinics in Japan regarding idiopathic sudden sensorineural hearing loss (SSNHL) revealed that the incidence of SSNHL was 60.9 per 100 000 population. There were more females than males in the younger generation. OBJECTIVE: The incidence of SSNHL varies largely by country. Because the Japanese criteria for diagnosing SSNHL have changed in accordance with those widely used in other parts of the world, a clinicoepidemiological study was undertaken using the new criteria. METHODS: Ehime, Aichi, and Iwate Prefectures were selected from the western, central, and northeastern regions of Japan, respectively. The subjects for this study were patients who suffered SSNHL between April 1, 2012 and March 31, 2013. Questionnaires were mailed to all hospitals and private clinics in which ENT doctors were working. Initial and final audiograms were requested for 10% of the patients. RESULTS: In all, 78 of 90 hospitals (87%) and 303 of 407 private clinics (74%) responded. It was reported that 1663 patients visited hospitals and 3090 patients visited only private clinics. It was estimated that 6205 SSNHL patients visited hospitals or private clinics in 1 year from a population of 10 145 000. Also, 23% of patients suffered acute low-tone SNHL (female to male ratio; 3:1 in definite cases).

Effect of clinical symptoms on the indication for selective neck dissection for N0 carcinomas of the parotid gland.

Lymph node metastasis is a major prognostic factor in parotid carcinoma, however, the pre-operative diagnosis of occult nodal metastasis is difficult in clinical N0 (cN0) parotid cancer patients. In addition, the indication of neck dissection in T1-3 cN0 patients is controversial. The current study investigated 17 patients with clinical T1-3 cN0 parotid cancer, and analyzed the correlation between patient symptoms/findings and pathological N status/tumor histological grade. In the statistical analysis, pain was found to significantly correlate with neck metastasis. Furthermore, cN0-staged patients without pain exhibited no neck metastasis. However, no significant correlation was identified between patient symptoms or findings and histological grade. These results indicate the possibility that selective neck dissection can be omitted for T1-3 cN0-staged patients without pain.

Endolymphatic hydrops revealed by magnetic resonance imaging in patients with acute low-tone sensorineural hearing loss.

OBJECTIVE: Acute low-tone sensorineural hearing loss (ALHL) has been reported to be associated with endolymphatic hydrops (EHs). However, evaluation of the size of the endolymphatic space has not been reported. We attempted to visualize EH in ALHL using magnetic resonance imaging (MRI). STUDY DESIGN: Prospective diagnostic study. SETTING: University hospital. METHODS: We evaluated 25 ears of 25 unilateral ALHL patients. Three-tesla MRI was obtained 24 hours after intratympanic injection of gadolinium (Gd) (n = 5) or 4 hours after intravenous injection of Gd (n = 20). A radiologist blinded to the patients' clinical data classified the degree of EH in the vestibule and cochlea into 3 groups: none, mild, and significant. RESULTS: On the affected sides, cochlear EH was recognized in 23 ears (92%) and was classified as significant EH (n = 15) or mild EH (n = 8); vestibular EH was detected in 22 ears (88%), classified as significant EH (n = 16) or mild EH (n = 6). Cochlear EH was more frequently observed in the affected ear than in the contralateral ear (90% versus 40%, p < 0.05). CONCLUSION: In ALHL, EH was observed not only in the cochlea but also in the vestibule as in Ménière's disease.

Magnetic resonance imaging of the inner ear after both intratympanic and intravenous gadolinium injections.

CONCLUSION: Using magnetic resonance imaging (MRI), endolymphatic hydrops could be visualized on both sides after intratympanic (IT) injection of gadolinium contrast agents (Gd) in one symptomatic ear and subsequent intravenous (IV) Gd injection. The MRI revealed a difference of intracochlear Gd distribution between the IT injection side and the contralateral IV side. OBJECTIVES: Although the IT method allows greater enhancement of the perilymph, many patients feel reluctance in receiving the IT injection in asymptomatic ears. We attempted to evaluate endolymphatic space size on both sides without the IT injection in asymptomatic ears. METHODS: In 10 patients with Meniere's disease, MRI was performed 24 h after the IT Gd injection in one symptomatic ear and 4 h after the IV Gd injection. The signal intensity of Gd in the basal and apical turns of the cochlea was evaluated. RESULTS: The signal intensity in the scala tympani of the basal turn of the cochlea was 1.70 ± 0.60 on the IT + IV side and 0.42 ± 0.10 on the contralateral (IV) side. Gd was distributed uniformly in the scala tympani in the cochlea on the IV side, whereas it was strongly localized in the basal turn on the IT + IV side.

Endolymphatic hydrops revealed by magnetic resonance imaging in patients with atypical Meniere's disease.

CONCLUSION: Our study showed that patients with atypical Meniere's disease had endolymphatic hydrops (EH) in both the cochlea and the vestibule. Using an imaging method, we provide evidence that atypical Meniere's disease is a true variant of classic Meniere's disease. OBJECTIVES: The aim of present study was to investigate images of the endolymphatic space in patients with atypical Meniere's disease (cochlear and vestibular Meniere's disease). METHODS: Sixty-four patients divided into two groups were enrolled in this study. The first group included 36 patients who had fluctuating hearing loss without vertigo, as candidates for cochlear Meniere's disease (CMD). The second group included 28 patients who had recurrent vertigo without hearing loss, as candidates for vestibular Meniere's disease (VMD). The patients underwent 3 T magnetic resonance imaging (MRI) after injection of gadolinium enhancement medium intratympanically or intravenously. We evaluated EH using MRI. RESULTS: Of 56 ears (36 patients) with CMD, 38 showed EH in the cochlea and 44 showed EH in the vestibule. Of 56 ears (28 patients) with VMD, 29 showed EH in the cochlea and 47 showed EH in the vestibule. The VMD group had a significant vestibular predominance in EH distribution whereas the CMD group showed no significant regional predominance of EH.

The NPC motif of aquaporin-11, unlike the NPA motif of known aquaporins, is essential for full expression of molecular function.

The recently identified molecule aquaporin-11 (AQP11) has a unique amino acid sequence pattern that includes an Asn-Pro-Cys (NPC) motif, corresponding to the N-terminal Asn-Pro-Ala (NPA) signature motif of conventional AQPs. In this study, we examined the effect of the mutation of the NPC motif on the subcellular localization, oligomerization, and water permeability of AQP11 in transfected mammalian cells. Furthermore, the effect was also assessed using zebrafish. Site-directed mutation at the NPC motif did not affect the subcellular localization of AQP11 but reduced its oligomerization. A cell swelling assay revealed that cells expressing AQP11 with a mutated NPC motif had significantly lower osmotic water permeability than cells expressing wild-type AQP11. Zebrafish deficient in endogenous AQP11 showed a deformity in the tail region at an early stage of development. This phenotype was dramatically rescued by injection of human wild-type AQP11 mRNA, whereas the effect of mRNA for AQP11 with a mutated NPC motif was less marked. Although the NPA motif is known to be important for formation of water-permeable pores by conventional AQPs, our observations suggest that the corresponding NPC motif of AQP11 is essential for full expression of molecular function.

Inhibitory effect of tyrphostin 47 on Shiga toxin-induced cell death.

The inhibitory effects of tyrosine kinase inhibitors including tyrphostins 25, 47 and 51 on Shiga toxin 1-induced cell death and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation were examined in Vero cells. Tyrphostin 47 significantly inhibited Shiga toxin 1-induced cell death and p38 MAPK phosphorylation. In contrast, tyrphostins 25 and 51 had no significant effect on the Shiga toxin 1-induced responses. These data indicate that Shiga toxin 1-induced cell injury occurs through a pathway sensitive to tyrphostin 47, and the target molecule for tyrphostin 47 opens up new opportunities for pharmacological intervention against Shiga toxin-producing Escherichia coli infectious diseases.

Disruption of aquaporin-11 produces polycystic kidneys following vacuolization of the proximal tubule.

Aquaporin-11 (AQP11) has been identified with unusual pore-forming NPA (asparagine-proline-alanine) boxes, but its function is unknown. We investigated its potential contribution to the kidney. Immunohistochemistry revealed that AQP11 was localized intracellularly in the proximal tubule. When AQP11 was transfected in CHO-K1 cells, it was localized in intracellular organelles. AQP11-null mice were generated; these mice exhibited vacuolization and cyst formation of the proximal tubule. AQP11-null mice were born normally but died before weaning due to advanced renal failure with polycystic kidneys, in which cysts occupied the whole cortex. Remarkably, cyst epithelia contained vacuoles. These vacuoles were present in the proximal tubules of newborn mice. In 3-week-old mice, these tubules contained multiple cysts. Primary cultured cells of the proximal tubule revealed an endosomal acidification defect in AQP11-null mice. These data demonstrate that AQP11 is essential for the proximal tubular function. AQP11-null mice are a novel model for polycystic kidney diseases and will provide a new mechanism for cystogenesis.