Characterization of the mouse DAX-1 gene reveals evolutionary conservation of a unique amino-terminal motif and widespread expression in mouse tissue.
The human genetic disorder adrenal hypoplasia congenita with hypogonadotropic hypogonadism results from mutations in the recently isolated DAX-1 gene, a member of the nuclear hormone receptor superfamily. To study the role of DAX-1 in adrenal development and activation of the hypothalamic pituitary-gonadal axis, animal model systems will be essential. Here, we report the isolation and characterization of the mouse DAX-1 gene and its tissue-specific pattern of expression. The mouse DAX-1 gene codes for a 472-amino acid protein, with 75% overall nucleotide sequence homology to its human homolog. The 3.5 amino-terminal repeats of a unique motif with probable DNA-binding activity have been conserved between mouse and human, although highest conservation in the DAX-1 peptide exists in the carboxy-terminal ligand-binding domain. The DAX-1 gene remains X-linked in the mouse, consistent with its potential role in sex determination. We have developed a sensitive reverse transcription-PCR assay that detects DAX-1 messenger RNA in the central nervous system, pituitary, lung, heart, spleen, kidney, and thymus in addition to the adrenal and testis DAX-1 expression noted for the human DAX-1 gene. Future studies using mouse models of altered DAX-1 expression will be critical in defining the role of this factor in tissue- and development-specific gene regulation.
Bae
D S
DS
Division of Endocrinology, Children's Hospital, Boston, Massachusetts 02115, USA.
Schaefer
M L
ML
Partan
B W
BW
Muglia
L
L
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D017124:Conserved Sequence; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D005796:Genes; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; C539966:Nr0b1 protein, mouse; D015345:Oligonucleotide Probes; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D014157:Transcription Factors