Mineral content of calcified tissues in cystic fibrosis mice

Although abnormal hard tissue mineralization is a recognized complication o f cystic fibrosis (CF), the pathogenesis leading from the defective cystic fibrosis transmembrane conductance regulator (CFTR) protein is poorly under stood. We hypothesized that CFTR plays a direct role in the mineralization of bone and teeth and tested the hypothesis using CF mouse models [CFTR(-) mice]. In vivo measurements by dual-emission X-ray absorpitometry (DEXA) in dicated that bone mineral density (BMD) was reduced in CF mice as compared to gender-matched littermates. However, no change was evident after correct ion of BMD for the covariant of body weight. The latter finding was confirm ed in isolated femurs and nasal bones by standard dry-ashing and instrument al neutron activation analysis (INAA). INAA of the continuously growing hyp sodont incisor teeth from CFTR(-) mice revealed reduced Ca and normal P in the enamel layer-a finding consistent with changes in the deciduous teeth o f CF children. Interestingly, enamel fluoride was increased in the CFTR(-) incisors and may associate with abnormal enamel crystallite formation. The iron content of the incisor enamel was reduced, explaining the loss of yell ow pigmentation in CFTR(-) incisors. In contrast to the incisors, the miner al content of the slow-growing brachydont molar teeth was not different bet ween CFTR(-) and CFTR(+) mice. It was concluded that CFTR does not play a d irect role in the mineralization of bones or brachydont teeth in mice. Func tional CFTR is apparently required for normal mineralization of the hypsodo nt incisors. However, multiple changes in the mineral composition of the CF incisors suggest an indirect role for CFTR, perhaps by maintaining a norma l salivary environment for continuous tooth eruption.