Characterization of genetically engineered mouse models carrying Col2a1-cre-induced deletions of Lrp5 and/or Lrp6

Abstract

Mice carrying Collagen2a1-cre-mediated deletions of Lrp5 and/or Lrp6 were created and characterized. Mice lacking either gene alone were viable and fertile with normal knee morphology. Mice in which both Lrp5 and Lrp6 were conditionally ablated via Collagen2a1-cre-mediated deletion displayed severe defects in skeletal development during embryogenesis. In addition, adult mice carrying Collagen2a1-cre-mediated deletions of Lrp5 and/or Lrp6 displayed low bone mass suggesting that the Collagen2a1-cre transgene was active in cells that subsequently differentiated into osteoblasts. In both embryonic skeletal development and establishment of adult bone mass, Lrp5 and Lrp6 carry out redundant functions.

Embryonic development: Sorting out a pair of bone builders

Two proteins play overlapping and essential roles in the formation of the skeleton during embryonic development. Low-density lipoprotein-related receptors, Lrp5 and Lrp6, respond to signals responsible for bone development. Mice completely lacking either receptor protein exhibit serious or lethal developmental defects. Researchers led by Bart Williams of the Van Andel Research Institute in the USA have used a more focused approach to study Lrp5 and Lrp 6, using genetically modified mice in which these proteins are only absent from cartilage- and bone-forming cell types. The loss of both proteins is catastrophic, with mice perishing before birth with severe skeletal abnormalities. Mice with localized loss of either Lrp5 or Lrp6 survive to adulthood, albeit with reduced bone mass, indicating that these proteins essentially act redundantly to facilitate bone development in these cell types.

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