Related Experiment Video
Updated: Jun 1, 2026
06:41
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Hypogonadotropic hypogonadism in subjects with DAX1 mutations
Unmesh Jadhav1, Rebecca M Harris, J Larry Jameson
1Division of Endocrinology, Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
Molecular and Cellular Endocrinology
|June 16, 2011
Summary
DAX1 mutations cause adrenal hypoplasia congenita and hypogonadotropic hypogonadism in boys. This gene is crucial for adrenal development, puberty, and maintaining pluripotency in embryonic stem cells.
Area of Science:
- Endocrinology
- Developmental Biology
- Genetics
Background:
- DAX1 (NROB1) encodes a nuclear receptor critical for development.
- Mutations in DAX1 cause X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HHG).
- DAX1 is expressed in adrenal glands, gonads, hypothalamus, pituitary, and embryonic stem cells.
Purpose of the Study:
- To review clinical manifestations of DAX1 mutations.
- To summarize functional roles of DAX1 in development and disease.
- To discuss findings from animal models and in vitro studies.
Main Methods:
- Review of clinical data from patients with DAX1 mutations.
- Analysis of data from animal models of DAX1 deficiency.
- In vitro studies investigating DAX1's molecular function.
Main Results:
- DAX1 mutations lead to adrenal failure and delayed puberty due to impaired adrenal development and hypogonadotropic hypogonadism.
- DAX1 acts as a transcriptional repressor, influencing pathways regulated by other nuclear receptors like SF1.
- DAX1 is essential for maintaining pluripotency in embryonic stem cells.
Conclusions:
- DAX1 is a key regulator of adrenal and gonadal development, as well as embryonic stem cell pluripotency.
- Understanding DAX1 function is vital for diagnosing and managing AHC and related disorders.
- Further research into DAX1's mechanisms will illuminate its broader roles in human development and disease.
Related Concept Videos
01:43Sex-linked Disorders
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
02:50Dosage Compensation
In animals, gender is determined by the number and type of sex chromosome. For example, human females have two X chromosomes, and males have one X and one Y chromosome, whereas C.elegans with one X chromosome is a male, and the one with two X chromosomes is a hermaphrodite.
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...
02:45The Ratio of X Chromosome to Autosomes
In most organisms, sex is determined by the ratio of X and Y chromosomes. However, in some organisms, such as Drosophila and C.elegans, sex is determined by the ratio of the number of X chromosomes to the number of sets of autosomes. The Y chromosome in Drosophila is active but does not determine sex. It contains genes responsible for the production of sperms in adult flies.
Normal male Drosophila has a ratio of one X chromosome to two sets of autosomes. In contrast, normal female Drosophila...
Normal male Drosophila has a ratio of one X chromosome to two sets of autosomes. In contrast, normal female Drosophila...
02:32Exon Recombination
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Exon shuffling follows “splice frame rules.” Each exon has three reading...
01:19X-linked Traits
In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
02:19The Y Chromosome Determines Maleness
The Y chromosome is a sex chromosome found in several vertebrates and mammals, including humans. In addition to 22 pairs of autosomes, the human males have one X chromosome and one Y chromosome. In these organisms, the presence or absence of the Y chromosome determines the development of male traits.
Evolution
Around 300 million years ago, the two sex chromosomes diverged from two identical autosomal chromosomes. Over time, the Y chromosome has lost most of its genes, shrinking in size. Today,...
Evolution
Around 300 million years ago, the two sex chromosomes diverged from two identical autosomal chromosomes. Over time, the Y chromosome has lost most of its genes, shrinking in size. Today,...