Joel Abramowitz (NIEHS)
Lutz Birnbaumer (NIEHS)
- The Go-α flox mice can be used to identify unknown biomedical functions of Go-α. Thus the mice could be used in developing therapeutics, diagnosis of disease, drug screening, assay development and as a research tool.
- The Gi2α mice can be used to identify unknown biomedical functions of Gi2α. Thus the mice could be used in developing therapeutics, diagnosis of disease, drug screening, assay development and as a research tool.
Heterotrimeric G proteins couple signals between GPCRs (G protein coupled receptors) and effectors such as adenylyl cyclase, phospholipase C and ion channels. Among the G proteins are Go and Gi2. Go is highly expressed in the brain and some endocrine tissues while Gi2 is widely expressed throughout the body. The βγ-subunits of Go interact with ion channels, and the α subunit has been shown to inhibit adenylyl cyclase. However a physiological role of the Gi2α has not been determined in a tissue specific manner.
In this invention, mice with a floxed allele of the Go-α subunit and mice with a floxed allele of the Gi2α subunit were generated. These transgenic mice can be used to study the function of Go-α and the function of Gi2α in a tissue specific manner.
- Mice in which Go-α has been globally deleted do not grow well and many die early after birth making it difficult to identify specific functions for Go-α. Using this mouse with floxed allele of Go-α would circumvent these problems.
- Mice in which Gi2α has been globally deleted are immune compromised and do not reproduce complicating the identification of tissue or cell specific Gi2α-dependent processes. Using this mouse with a floxed allele of Gi2α would circumvent these problems.