TIMP-2^-/- mice were created by deletion of exon 1 that contains the signal sequence for secretion and the cysteine residue that allows TIMP-2 to bind to and inhibit metzincins. To our surprise, TIMP-2^-/- mice contain mRNA and protein for TIMP-2 exons 2-5. The first intron of TIMP-2 contains the nested gene DDC8 that was previously reported to be testis-specific. However, we have shown that DDC8 is not restricted to the testis. Rather, DDC8 expression in neural and non-neural tissues mimics that of TIMP-2. Strikingly, like TIMP-2, DDC8 is up-regulated in response to traumatic brain injury, suggesting a common regulatory mechanism. Studies are currently in progress to isolate and characterize the function of DDC8
and the DDC8-TIMP-2 splice variant during
nervous system development and injury.