Figure 4.

PHP antibodies bind to mHTT assemblies in the brains of HD mice. (A) WB analysis of cortical lysates of N-586 HD mice harvested at 3, 5 and 7 months (m) of age and probed with PHP1 and PHP2 (top and bottom panels, respectively). Cortical lysates of 3-month-old WT mice were used as controls. Arrows point to monomeric N-586 (82Q) detected by each antibody. Brackets are the mHTT assemblies present in the brain lysate of 5-month and 7-month-old N-586 HD mice, which are less abundant in the 3-month olds. Part (B) is WB analysis of the same lysates probed by PHP3 and PHP4. Both antibodies react with monomeric N-586 fragment and some smaller products highlighted by asterisks. N.S., non-specific bands. The house keeping protein glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as a loading control. Lysates obtained from brains of offspring from various cohorts revealed similar results.