In vivo characterization of skeletal phenotype of genetically modified mice.
Genetically modified mouse models provide an important tool for understanding of the roles of specific gene in skeletal growth, development, and aging. Appropriate study design is essential for characterization of skeletal phenotype of these mice. It is important to characterize the bone status of the different phases of skeletal development including the early rapid growth, attainment of peak bone mass, and age-related bone loss phases. In C57BL/6 strain mice, cancellous and cortical bone mass rapidly increases with age before 3 months of age, and reaches the peak cancellous bone mass at approximately 6-8 months of age, while cortical bone mass continuously increases until 12 months of age. Thereafter, age-related decrease in bone mass occurs. According to these observations, at least three different age groups need to be evaluated for bone status to cover the different phases of the life span: 1-3 months of age for rapid growth, 6-9 months for peak bone mass, and >12 months for aged phases. Furthermore, bone resorption and formation activities on all bone surfaces (periosteal, endocortical, intracortical, and cancellous) need to be evaluated. In this article, we briefly summarize our findings in the estrogen receptor-beta knockout (BERKO) and the P2X7 receptor (an ATP-gated ion channel) knockout mice. In BERKO female mice, bone status at 6, 13, and 21 months of ages was evaluated as compared with the wild-type littermate controls. We found that estrogen receptor-beta plays an inhibitory role in periosteal bone formation and longitudinal and radial growth during the growth period, whereas it plays a role in stimulation of bone resorption, bone turnover, and bone loss on cancellous and endocortical bone surfaces during the aging process. We also found that ER-beta knockout improves the survival rate between 6 and 21 months of age. In P2X7R knockout mice, bone status at 2, 5, 9, and 15 months of age was evaluated for both sexes as compared with their wild-type littermate controls. We found that P2X7R plays a role in stimulating periosteal and cancellous bone formation and inhibiting cancellous bone resorption during the growth period.
Ke
Hua Zhu
HZ
Osteoporosis Research, Mail Stop 8118W-216, Pfizer Global Research and Development, Groton Laboratories, Groton, CT 06340, USA. huazhu_ke@groton.pfizer.com
D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D047629:Estrogen Receptor beta / Q000172:deficiency / Q000378:metabolism*; D005260:Female; D005269:Femur / Q000254:growth & development* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D018048:Receptors, Purinergic P2 / Q000172:deficiency / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D013977:Tibia / Q000254:growth & development* / Q000473:pathology
D047629:Estrogen Receptor beta; C546469:P2rx7 protein, mouse; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7