Abstract
Across the world, dozens of outbred Hartley guinea pig stocks are used for auditory experiments. The genetic makeup of these different stocks will differ due to differences in breeding protocols, history and genetic drift. In fact, outbred breeding protocols are not intended to produce genetically identical animals, neither across breeders, nor across time. For this reason, it is unclear how reproducible experimental results are likely to be using animals from different stocks. We evaluated the consistency of cochlear function using both clicks and tones in Hartley guinea pigs as a function of breeder (Kuiper and Charles River) and sex using archival Auditory Brain Stem Response (ABR) data and tissue from our own laboratory. Sound levels required to reach baseline threshold for click-induced ABRs were similar between male Charles River and male Kuiper guinea pig stocks. However, the median and average thresholds after exposure to high level noise were larger in the Kuiper population than in the Charles River population with corresponding threshold shifts higher in the Kuiper than in the Charles River animals. We evaluated the relationship between pure-tone thresholds and sex, age, breeder stock, left or right cochleas, weight and 5 test frequencies before and after noise exposure using a linear mixed statistical model. Across all frequencies, the effect of breeder on baseline threshold is statistically significant, with effect sizes most pronounced at the lower frequencies before exposure to noise. After noise exposure, the differences are minimal in the model, indicating that differences in threshold shift are chiefly due to differences in initial baseline hearing. However, a contingency calculation comparing response/no response at the highest speaker output at 32 kHz gave a statistically significant difference between the stocks: 28% of Kuiper cochleas responded to the highest output of the speaker as compared with 71.4% of Charles River cochleas, indicating that noise exposure induced a larger threshold shift in a greater proportion of Kuiper animals. Using our archival cochlear tissue from these studies, we confirmed the sex of each animal by PCR, then compared males and females of the Kuiper stock. Across all baseline frequencies, the effect of sex on threshold is statistically significant, with no noticeable difference after exposure. The effect sizes for baseline thresholds are most pronounced at lower frequencies. These data demonstrate that Hartley guinea pig stocks from different breeders are not uniform in their auditory characteristics, and that due to these differences, results and conclusions can differ among laboratories. Moreover, within a single stock, males and females can provide different data, confirming that male and female animals must be individually evaluated in any auditory protocol.
Original language | English (US) |
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Pages (from-to) | 69-78 |
Number of pages | 10 |
Journal | Hearing research |
Volume | 379 |
DOIs | |
State | Published - Aug 2019 |
Funding
We appreciate the discussions on inbred and outbred animals and comments on the manuscript made by Dr. Michael Festing and Dr. Kevin Ohlemiller on the characteristics of inbred lines and outbred stocks. We thank Drs. Sumit Dhar and Judy Dubno for advice on linear mixed models. We thank Mr. Terry Kuiper for sharing the history of the Kuiper guinea pig stock and Charles River Laboratories for providing information on their guinea pigs. We thank Mary Grover for tabulating the published guinea pig data. This work was supported by grants from the Office of Naval Research #N000141210173 ; N000141512130 ; N000141612508 and by the Department of Otolaryngology-Head and Neck Surgery , Feinberg School of Medicine, Northwestern University .
Keywords
- ABR
- Guinea pig
- Hearing
- Linear mixed model
- Noise-induced threshold shifts
- Outbred
- Sex
ASJC Scopus subject areas
- Sensory Systems