ARTICLE Addressing Animal Model Issues in Auditory Research Saad Alsaleh, MD, Brian W. Blakley, MD, PhD, FRCSC, FACS, Eric Meen, MD, and Zameel Dewji, MD ABSTRACT Objective: To better understand the differences in auditory systems across species. Methods: Auditory brainstem response (ABR) click thresholds were obtained from normal 3- to 6-week-old animals including 15 guinea pigs, 62 mice, and 6 rats. Pure-tone ABR thresholds were obtained in 7 guinea pigs, 6 mice, and 13 rats. Threshold variability was then considered a function of basilar membrane length, mean body weight, basal metabolic rate, and longevity as identified in the literature. Results: Interspecies variability of auditory thresholds for normal-hearing animals is not explained by differences in mean body weight, metabolic rate, or longevity. Simple linear models appear to adequately describe threshold variability across the parameters studied. Click thresholds, with significant low-frequency content, suggest that mice have better hearing than rats or guinea pigs. Conclusion: In spite of wide variations in cochlear anatomy and metabolic factors, different species have evolved similar auditory thresholds across species in normal, young animals. SOMMAIRE Objectif: L'étude avait pour objectif de faire ressortir les différences de l'appareil auditif entre des espèces. Méthodes: Nous avons établi des seuils de réponses évoquées auditives du tronc cérébral (REATC) au clic, chez des animaux normaux, âgés de 3 à 6 semaines, soit chez 15 cobayes, 62 souris et 6 rats, puis nous avons établi des seuils de REATC en son pur chez 7 cobayes, 6 souris et 13 rats. La variabilité des seuils a ensuite été considérée comme une fonction de la longueur de la membrane basilaire, du poids corporel moyen, de la vitesse du métabolisme basai et de la longévité, comme en faisait état la documentation. Résultats: La variabilité des seuils d'audition, entre les espèces, chez les animaux ayant une audition normale ne s'explique pas par les différences de poids corporel moyen, de vitesse du métabolisme basai ou de longévité. De simples modèles linéaires semblent bien décrire la variabilité des seuils observée pour les paramètres étudiés. Les seuils d'audition au clic, ayant un contenu riche en basses fréquences, donnent à penser que les souris sont dotées d'une meilleure audition que les rats ou les cobayes. Conclusion: Malgré des différences importantes d'anatomie de la cochlée et de facteurs métaboliques, les différentes espèces ont développé des seuils d'audition comparables entre elles, parmi les jeunes animaux normaux. Key words: cisplatin, drugs, guinea pig, hearing loss, mice, ototoxiclty, rat, therapeutics A nimals are frequently used in research as models for human physiology, but evaluation of data often reveals inconsistent findings across species. This article contrasts normal auditory thresholds across the three species most commonly used in ear research—guinea pigs. Saad Alsaleh, Brian W. Blakley, Eric Meen, and Zameel Dewji: Department of Otolaryngology, University of Manitoba, Winnipeg, MB. Presented at the Poliquin Resident Research Competition, 64th annual meeting of the Canadian Society of Otolaryngology-Head and Neck Surgery, Niagara Falls, ON, May 24, 2010. Address reprint requests to: Brian W. Blakley, MD, PhD, FRCSC, FACS, Department of Otolaryngology, Health Sciences Centre, University of Manitoba, GB42I-820 Sherbrook Street, Winnipeg, MB R3A IR9; e-mail: bblakley&exchange. hsc. mb.ca. DOI 10.2310/7070.2011,100085 i( 2011 The Canadian Society of Otolaryngology-Head & Neck Surgery rats, and mice—and seeks to explain the differences observed. Such knowledge could very well benefit our knowledge of human physiology. One obvious possible determinant of cochlear sensi- tivity across species is cochlear anatomy. Of the possible anatomic measurements that could be considered, the length of the basilar membrane seems to be most directly related to threshold. We hypothesized that short basilar membranes would have greater sensitivity in higher frequencies than longer ones. Another possible determinant of auditory sensitivity is metabolic rate. We hypothesized that a high metabolic rate would be required to maintain auditory sensitivity, particularly for high-frequency sound. Metabolic rate is a function of body mass. Kleiber's law is a well-known, general, cross-species statement that basal metabolic rate is proportional to the 0.75 power of body mass across many Journal of Otolaryngology-Head & Neck Surgery, Vol 40, No SI (February), 2011: pp S41-S44 841