Postnatal Conditional Knockout of Bcl11b in Striatal Projection Neurons Mimics the Transcriptional Signature of Huntington's Disease

Dysregulation of the striatum is linked to multiple diseases including Huntington's (HD), Parkinson's, X-linked dystonia-parkinsonism (XDP), addiction, autism, and schizophrenia. Striatal medium spiny neurons (MSNs) make up 90% of the neuronal cell type in the striatum and are critical to motor control. The transcription factor Bcl11b (also known as CTIP2) is known to regulate of MSN differentiation, striatal striosome (patch) development and the architecture of the striatum during development. However, the function of Bcl11b adult striatal neurons in vivo has not been investigated. Therefore, we conditionally knocked out Bcl11b specifically in MSNs using D9-cre under the control of a regulatory elements of the mouse Ppp1r1b gene encoding DARPP-32 resulting in knockout around 5-6 weeks of age. Transcriptomic and behavioral analysis were performed on these mice. RNA-Seq analysis of the mouse striatum of 4 D9-Cre-Bcl11b tm1.1 Lead mice and Cre- mice have reduced expression of Bcl11b in the striatum at 4 months of age.