These tetO-CDK5R1* mice express a truncated human cyclin-dependent kinase 5, regulatory subunit 1 (CDKR1 or p35) cDNA sequence, also referred to as p25, under the control of a tetracycline operator (tetO; also called tetracycline-responsive element (TRE, TetRE) or tet-operator). The N-terminal truncated isoform of p35 is p25. Unlike p35, which is membrane bound in postmitotic neurons in the brain, p25 is non-tethered and expression is seen in all cellular compartments of neuronal somata and dendrites. Mice that are hemizygous for this transgene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When bred with another mouse expressing reverse tetracycline-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA), CDK5R1 expression can be regulated with the tetracycline analog doxycycline (dox) in the resulting double mutant offspring. For example, when bred to a strain expressing a CaMKII-tTA transgene expressed in forebrain neurons, the neuronal expression of human p25 causes extensive neurodegeneration and neuroinflammation, resulting in loss of neurons in hippocampus and cortex and in severe brain atrophy. This leads to postnatal (pre-weaning) lethality in double transgenics, which can be rescued by administering dox to dams and pups for the first 6 weeks of life. As soon as 2 weeks following withdrawal of dox, neurodegeneration is evident with a vast degeneration of the hippocampus, while the forebrain olfactory bulb and cerebellum remain normal. These tetO-CDK5R1* mice may be used in generating bi-transgenic mutant mice for the reversible, inducible expression of p25 in specific groups of cells. They may be useful for studying neurodegeneration and neuroinflammation associated with Alzheimer's Disease, hippocampal sclerosis, and other brain disorders.

These tetO-CDK5R1* mice express a truncated human cyclin-dependent kinase 5, regulatory subunit 1 (CDKR1 or p35) cDNA sequence, under the control of a tetracycline operator (tetO. These tetO-CDK5R1* mice may be used in generating bi-transgenic mutant mice for the reversible, inducible expression of p25 in specific groups of cells. They may be useful for studying neurodegeneration and neuroinflammation associated with Alzheimer's Disease, hippocampal sclerosis, and other brain disorders.

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