For the analysis of Mendelian segregation of alleles, sample size was determined by power analysis using http://biomath.info/power/chsq1gp.htm. Sufficient mice to detect a 50% reduction in expected frequency were used, using power of 0.8 and alpha 0.05. No statistical methods were used to predetermine sample size in the other animal experiments. No randomization was employed. The investigators were blinded to the genotypes of mice throughout the study and data were acquired by relying purely on identification numbers.