A Phenotypic Atlas for Huntington Disease Based on Data From the Enroll-HD Cohort Study.

Background And Objectives: The variable CAG repeat expansion in the huntingtin gene and its inverse relationship to motor dysfunction onset are fundamental features of Huntington disease (HD). However, the wider phenotype (including non-motor features) at particular CAG lengths, ages, and functional levels is less well-characterized. The large number of participants in the Enroll-HD observational study enables the development of a phenotype atlas that summarizes the range and distribution of HD phenotypes, including outliers and possible clusters, with respect to various CAG repeat lengths, age ranges, and declining functional levels.

Mutant human cells with constitutive activation of NF-kappaB.

We have used a genetic approach to generate eight different mutant human cell lines in which NF-kappaB is constitutively activated. These independent clones have different phenotypes and belong to several different genetic complementation groups. In one clone inhibitor of kappaB(IkappaB) kinase is constitutively active, but in the seven others it is not, despite the fact that IkappaB is degraded in all eight clones.

Secretion of cytokines and growth factors as a general cause of constitutive NFkappaB activation in cancer.

The constitutive activation of nuclear factor kappaB (NFkappaB) helps a variety of tumors to resist apoptosis and desensitizes them to chemotherapy, but the causes are still largely unknown. We have analysed this phenomenon in eight mutant cell lines derived from human 293 cells, selected for NFkappaB-dependent expression of a marker gene, and also in seven tumor-derived cell lines. Conditioned media from all of these cells stimulated the activation of NFkappaB (up to 30-fold) in indicator cells carrying an NFkappaB-responsive reporter.