Genetic Regulation of Chemoreceptor Development in DBA/2J and A/J Strains of Mice

Abstract

The role of the carotid body (CB) in response to hypoxia is very well defined (Fitzgerald and Shirahata, 1997). The hypoxic ventilatory response (HVR) is characterized by an increase in ventilation, but this response remains variable among individuals (Eisele et al., 1992; Vizek et al., 1987; Weil 1970). Genetics may play a critical role in explaining this variability. Indeed, longitudinal and twin studies do demonstrate the role of genetics in the HVR (Collins et al., 1978; Kawakami et al., 1982). Studies utilizing inbred strains of mice have also demonstrated the effect of genetics on the response to hypoxia (Tankersley et al., 1994 & 2000). Two strains of mice in these studies were identified as having extreme responses to hypoxia. The DBA/2J strain demonstrated the highest HVR, whereas the A/J strain demonstrated the lowest HVR (Tankersley et al., 1994). In another study analyzing the role of genetics in a mouse model of sleepinduced hypoxia, the DBA/2J strain demonstrated an increased sensitivity to hypoxia during sleep, compared to that of the A/J strain (Rubin et al., 2004). In order to elucidate a potential explanation that may contribute to this difference in hypoxic sensitivity, we examined CB morphology and volume in adult DBA/2J and A/J strains (Yamaguchi et al., 2003). Results demonstrated a significantly larger volume as well as an increased glomus cell quantity in the CB of DBA/2J strain compared to that of the A/J strain. A question arises whether these differences exist from early neonatal ages. Or, developmental plasticity may contribute to these strain differences. In this study, we analyzed CB volume, glomus cell quantity, and ventilation during development in the DBA/2J and A/J strains of mice. We also introduced a glimpse into the genetic influence on chemoreceptor development with emphasis on the role of glial-cell-line-derived neurotrophic factor (GDNF).