(A) Heterozygous SD-B, SD-C and SA transgenes were bred in two successive generations with murine Hdh heterozygous knockout mice(Zeitlin et al., 1995) to generate the rescue mice (i.e. fl-mhtt transgene rescue the embryonic lethality of htt null mice). Since the homozygous Hdh null mice are embryonic lethal (ibid), the expected ratio of rescue mice among the live mice born is 1 out of 7. The rescue mice for SD-B, SD-C and SA were born with such Mendelian ratio. (B and C) Western blot analyses with mAb2166 (Htt) and 1C2 to confirm the rescue mice only express fl-mhtt and lack endogenous murine htt. (D–G) SD fl-mhtt retains the essential adult neuronal function of htt in vivo. Nissl stained coronal brain sections of 12-month old SD-B rescue mice (F and G) and WT littermates (D and E) at two different magnifications. No evidence of late-onset cortical neurodegeneration, as previously reported in the forebrain-specific htt null mice (Dragtsis et al, 2000), was detected in these rescue mice. Scale bars = 50 μm.