INNOVATION:  UCLA researchers have generated novel mouse models of HD using Bacterial Artificial Chromosome (BAC) transgenic technology. Western blot analyses demonstrate that the transgenic mice broadly express full length mhtt in the brain at approximately the same level as the endogenous murine wildtype htt. These mice exhibit progressive and robust motor deficits demonstrated by Rotarod and open field tests. These mice accumulate mhtt aggregates and inclusions in a brain and subcellular distribution pattern similar to that of HD patients. Neuropathological studies demonstrated that these mice exhibit highly selective brain atrophy and neurodegeneration in the cortex and striatum, but not in other brain regions spared in HD. Therefore, these mice represent a robust full length mouse model suitable to study HD pathogenesis and to test therapeutic compounds and strategies for HD.

POTENTIAL APPLICATIONS 

• Transgenic HD mice can be used to study the pathogenesis of HD.
• Transgenic HD mice can be utilized to test therapeutic compounds and strategies for HD.

ADVANTAGES

• BAC transgenic system can consistently produce high levels of and endogenous-like transgene expression in vivo.
• Transgenic HD mice exhibit progressive and robust motor deficiencies as compared to other mouse models.
• Transgenic HD mice display neuropathology which is strikingly similar to HD patients.

Reference: UCLA Case No. 2005-492