HIGHLIGHT Targeted disruption of the Ahch (Dax-1) gene: knockout of old concepts

Mutations in the human transcription factor AHC cause the X-linked recessive form of adrenal hypoplasia congenita (1–3). Boys with adrenal hypoplasia con-genita present with cortisol and mineralocorticoid deficiency in early childhood, and they fail to undergo puberty due to hypogonadotropic hypogonadism (HHG) (3, 4). In addition, a subset of these patients has a contiguous gene deletion syndrome involving several X-chromosomal genes (glycerol kinase deficiency, Duchenne muscular dystrophy, ornithine transcarbamoyl transferase deficiency, mental retardation). Duplication of the AHC locus on chromosome Xp21 also has dramatic consequences and results in a female pheno-type in 46XY males, a mechanism referred to as ‘dosage sensitive sex reversal’. The AHC gene, initially calle