Abstract
In addition to xeroderma pigmentosum (XP), mutations in the human XPG gene cause an early onset of Cockayne syndrome (CS) in some patients (XPG/CS) with characteristics such as growth retardation and a short life span. To identify the XPG region that causes the onset of CS, we have generated Xpg mutant mice with C-terminal truncations or a base substitution mutation, and examined their growth and life span. The CS-causing mutation XpgD811stop completely inhibited the NER activity of Xpg, but the non-CS causing mutations, XpgD811A or Xpgdelex15 (deletion of the last 183 amino acids), resulted in the retention of residual NER activity. To generate a completely defective NER condition in mice with the non-CS causing Xpg mutation we crossed these mutant mice with Xpa-null mutant mice. When the Xpa-null mutant allele was introduced, mice with the non-CS causing deletion mutation (Xpgdelex15) exhibited the CS phenotype (growth retardation and short life span), but the base substitution mutant (XpgD811A) mice did not. These results indicate that both the C-terminal truncation of Xpg and a complete loss of NER activity are required for the expression of the CS phenotype.
