Increased early striatal cell death and HD-like neurochemical changes in Hip14−/− mice. (Ai) No differences in LGE volumes were observed in E12.5, and (Aii) E14.5 Hip14−/− embryos (n= 5). (Aiii) However, a significant decrease in striatal volume was observed at E17.5 (n= 5). (B) Pregnant females were injected with BrdU, and numbers of BrdU-positive cells were assessed in the LGE of (i) day 12.5 in utero (E12.5) and (ii) E14.5 pups. No differences in number of BrdU-positive cells were observed (n= 6). (C) Adjacent sections were stained for TUNEL to assess apoptosis. (i) No difference was observed in the number of TUNEL-positive striatal neurons at E12.5 (n= 6). However, (ii) a significant increase in the number of TUNEL-positive striatal neurons undergoing apoptosis was observed in E14.5 Hip14−/− embryos (n = 7). (D and E) The majority of MSNs express high levels of DARPP32. DARPP32 levels were significantly decreased in 3-month-old Hip14−/− striatum (n = 7). (F and G) Of the DARPP32-containing neurons, the subset expressing enkephalin is predominantly affected in HD. Similarly, enkephalin levels were significantly decreased in the Hip14−/− striatum. (H and I) No changes in substance P levels were observed in the MSNs of Hip14−/− mice (n = 7).