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Document Type
Oral Presentation
Department
Biological Sciences
Faculty Mentor
David Champlin, PhD
Keywords
Trpm8, bone, osteoblast, Cre, loxP, mouse models, dorsal root ganglia
Abstract
Recent studies suggest that the use of thermoregulatory treatments that affect brown fat may help curb obesity. However it is unknown how these treatments may affect bone homeostasis. Our work has focused on the transient receptor potential melastatin (TRPM8) protein, which is responsible for detecting colder temperatures in sensory neurons. Previous work within the Motyl laboratory has found that Trpm8 plays a role in bone acquisition. Mice with a global deletion of the Trpm8 gene have reduced trabecular bone volume fraction due to reduced bone formation by osteoblasts. However, it is unclear whether sensory neuron or osteoblast-mediated expression of Trpm8 is responsible for this finding. To test this, we generated mice with loxP sites surrounding the Trpm8 gene. Using a constitutively expressed Cre, we generated a global knockout mouse model to confirm that the DNA in the new mouse model recombines as expected and that the global deletion of Trpm8 suppresses bone volume fraction and bone formation. Our aim is to confirm the Trpm8 deletion by examining gene expression in the dorsal root ganglion. We will also examine the low bone mass phenotype using micro-computed tomography and dual energy x-ray absorptiometry. Future work will use the Trpm8 sensory-neuron specific deletion to test the hypothesis that cold-temperature sensation supports bone homeostasis.
Validation of a novel Trpm8 knockout mouse model - transcript
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Validation of a novel Trpm8 knockout mouse model
Recent studies suggest that the use of thermoregulatory treatments that affect brown fat may help curb obesity. However it is unknown how these treatments may affect bone homeostasis. Our work has focused on the transient receptor potential melastatin (TRPM8) protein, which is responsible for detecting colder temperatures in sensory neurons. Previous work within the Motyl laboratory has found that Trpm8 plays a role in bone acquisition. Mice with a global deletion of the Trpm8 gene have reduced trabecular bone volume fraction due to reduced bone formation by osteoblasts. However, it is unclear whether sensory neuron or osteoblast-mediated expression of Trpm8 is responsible for this finding. To test this, we generated mice with loxP sites surrounding the Trpm8 gene. Using a constitutively expressed Cre, we generated a global knockout mouse model to confirm that the DNA in the new mouse model recombines as expected and that the global deletion of Trpm8 suppresses bone volume fraction and bone formation. Our aim is to confirm the Trpm8 deletion by examining gene expression in the dorsal root ganglion. We will also examine the low bone mass phenotype using micro-computed tomography and dual energy x-ray absorptiometry. Future work will use the Trpm8 sensory-neuron specific deletion to test the hypothesis that cold-temperature sensation supports bone homeostasis.
