• RBM3 upregulation reverses multiple tau phosphorylations post-TBI • Novel RBM3 Overexpressing Transgenic Mouse Model allows researchers to study the effects of RBM3 activation on tissue function, brain function, and brain injury
Traumatic brain injury (TBI) not only causes immediate neuronal damage but also predisposes survivors to chronic cognitive decline and Alzheimer-like pathology, including tau hyperphosphorylation, synapse loss and impaired learning and memory; USF researchers discovered that a brief, mild hypothermia pre-conditioning at 32–34 °C in mice rapidly induces neuronal expression of the RNA-binding motif protein RBM3, which in turn preserves hippocampal long-term potentiation, maintains dendritic spine density, prevents traumatic brain injury (TBI)–induced tau hyperphosphorylation, and rescues spatial learning and memory;
A transgenic RBM3 inducible mouse model was developed which allows researchers to re-activate RBM3 in tissues, including the brain and study the effects on neurobiology, brain function, and brain injury. It was engineered by incorporating the TRE3G-promoter drived RBM3 inducible construct into intron 1 of the ROSA26 sequence. Treatment of mice with doxycycline induces the TRE3G promoter, which then activates two copies of the RBM3 gene: The first copy encodes the wildtype RBM3 gene, the second copy encodes a 3X-FLAG tagged version of RBM3. LoxP sites have been introduced such that the sequnces can be removed from tissues with a CRE strain.
Hypothermia pre-treatment induces RBM3 expression in mice. The expression of the RBM3 in the extracts of hippocampi of mice was detected by Western blotting (A) and quantitative analysis (B). The representative immunostaining image.