Shirahata. Structural and functional differences of the carotid body between DBA/2J and A/J strains of mice. J Appl Physiol 94: 1536-1542, 2003; 10.1152/japplphysiol. 00739.2002.-In a previous study, DBA/2J and A/J inbred mice showed extremely different hypoxic ventilatory responses, suggesting variations in their carotid bodies. We have assessed the morphological and functional differences of the carotid bodies in these mice. Histological examination revealed a clearly delineated carotid body only in the DBA/2J mice. Many typical glomus cells and glomeruli appeared in the DBA/2J but not in the A/J mice. The size of the carotid body in the DBA/2J and A/J mice was 6.3 Ϯ 0.5 ϫ 10 6 and 1.5 Ϯ 0.3 ϫ 10 6 m 3 , respectively. The area immunostained for tyrosine hydroxylase, an estimation of the glomus cell quantity, was four times larger in the DBA/2J mice than in the A/J mice. The individual data points in the DBA/2J mice segregated from those in the A/J mice. ACh increased intracellular Ca 2ϩ in most clusters (81%) of cultured carotid body cells from the DBA/2J mice, but only in 18% of clusters in the A/J mice. These data suggest that genetic determinants account for the strain differences in the structure and function of the carotid body. genetic determinants; morphometry; immunocytochemistry; intracellular calcium; hypoxic ventilatory response THE CAROTID BODY IS A major player in the ventilatory responses to hypoxia (7,11,12). During hypoxia, the neural output from the carotid body increases and reflexly modifies several variables in the respiratory system. A prominent response is an increase in ventilation, but the hypoxic ventilatory response (HVR) among individuals varies widely (9,38,40). Studies with twins and longitudinal studies with the same individuals indicate that genetic factors significantly contribute to these differences in healthy humans (5,19,20,25,35). Recently, Tankersley et al. (33,34) demonstrated differential ventilatory responses to hypoxia among several inbred strains of mice, which indicates that genetic determinants robustly influenced HVR. They showed that the DBA/2J mice demonstrated the highest HVR and the A/J mice the lowest HVR (34). These data suggested that genetically regulated differences exist in the system controlling the HVR. The differences may be in the carotid body, chemoreceptor afferent, or the central integration network for hypoxia.Previous studies have suggested some correlation between the size of the carotid body and its function. For example, small carotid bodies were found in victims of sudden infant death syndrome (4, 24) and congenital hypoventilation syndrome (6). In these patients, HVR appears to be blunted (16,28). On the other hand, hypersensitivity of the carotid body has been reported in subjects with mild hypertension (17,36,37), and hypertrophy of the carotid body was noted in subjects with established hypertension (13, 15). Similarly, hypersensitivity of the carotid body to hypoxia and hyperoxia and enlargemant of the carotid body have been shown in sp...