BIOMAT Database Logo BIOMAT Database Logo

Gonadal sex reversal in mutant Dax1 XY mice: a failure to upregulate Sox9 in pre-Sertoli cells. 2005

Gerrit J Bouma, and Kenneth H Albrecht, and Linda L Washburn, and Andrew K Recknagel, and Gary A Churchill, and Eva M Eicher
The Jackson Laboratory, Bar Harbor, ME 04609, USA. jbouma@jax.org

The nuclear receptor transcription factor Dax1 is hypothesized to play a role in testicular development, although the mechanism of its action is unknown. Here, we present evidence that Dax1 plays an early essential role in fetal testis development. We hypothesize that upregulation of Sox9 expression in precursor somatic cells, a process required for their differentiation as Sertoli cells, depends on the coordinated expression of Dax1, Sry and another gene, Tda1. Our conclusion and model are based on the following experimental findings: (1) presence of a mutant Dax1 allele (Dax1-) results in complete gonadal sex reversal in C57BL/6JEi (B6) XY mice, whereas testes develop in DBA/2J (D2) and (B6xD2)F1 XY mice; (2) B6-DAX1 sex reversal is inherited as a complex trait that includes the chromosome 4 gene Tda1; (3) B6 Dax1-/Y fetal gonads initiate development as ovaries, even though Sry expression is activated at the correct time and at appropriate levels; (4) upregulation of Sox9 does not occur in B6 Dax1-/Y fetal gonads in spite of apparently normal Sry expression; and (5) overexpression of Sry in B6 Dax1-/Y fetal gonads upregulates Sox9 and corrects testis development.

UI MeSH Term Description Entries
D008297 Male Males
D008806 Mice, Inbred AKR An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. Mice, AKR,Mouse, AKR,Mouse, Inbred AKR,AKR Mice,AKR Mice, Inbred,AKR Mouse,AKR Mouse, Inbred,Inbred AKR Mice,Inbred AKR Mouse
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008811 Mice, Inbred DBA An inbred strain of mouse. Specific substrains are used in a variety of areas of BIOMEDICAL RESEARCH such as DBA/1J, which is used as a model for RHEUMATOID ARTHRITIS. Mice, DBA,Mouse, DBA,Mouse, Inbred DBA,DBA Mice,DBA Mice, Inbred,DBA Mouse,DBA Mouse, Inbred,Inbred DBA Mice,Inbred DBA Mouse
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D009687 Nuclear Proteins Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D010053 Ovary The reproductive organ (GONADS) in female animals. In vertebrates, the ovary contains two functional parts: the OVARIAN FOLLICLE for the production of female germ cells (OOGENESIS); and the endocrine cells (GRANULOSA CELLS; THECA CELLS; and LUTEAL CELLS) for the production of ESTROGENS and PROGESTERONE. Ovaries
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins

Related Publications

Gerrit J Bouma, and Kenneth H Albrecht, and Linda L Washburn, and Andrew K Recknagel, and Gary A Churchill, and Eva M Eicher
Disturbed expression of Sox9 in pre-sertoli cells underlies sex-reversal in mice b6.Ytir.
January 2004, Biology of reproduction,
Gerrit J Bouma, and Kenneth H Albrecht, and Linda L Washburn, and Andrew K Recknagel, and Gary A Churchill, and Eva M Eicher
Homozygous inactivation of Sox9 causes complete XY sex reversal in mice.
January 2006, Biology of reproduction,
Gerrit J Bouma, and Kenneth H Albrecht, and Linda L Washburn, and Andrew K Recknagel, and Gary A Churchill, and Eva M Eicher
A novel mouse Fgfr2 mutant, hobbyhorse (hob), exhibits complete XY gonadal sex reversal.
January 2014, PloS one,
Gerrit J Bouma, and Kenneth H Albrecht, and Linda L Washburn, and Andrew K Recknagel, and Gary A Churchill, and Eva M Eicher
Loss of NEDD4 causes complete XY gonadal sex reversal in mice.
January 2022, Cell death & disease,
Gerrit J Bouma, and Kenneth H Albrecht, and Linda L Washburn, and Andrew K Recknagel, and Gary A Churchill, and Eva M Eicher
XY sex reversal and gonadal dysgenesis due to 9p24 monosomy.
December 1997, American journal of medical genetics,
Gerrit J Bouma, and Kenneth H Albrecht, and Linda L Washburn, and Andrew K Recknagel, and Gary A Churchill, and Eva M Eicher
SRY, SOX9, and DAX1 expression patterns during human sex determination and gonadal development.
March 2000, Mechanisms of development,
Gerrit J Bouma, and Kenneth H Albrecht, and Linda L Washburn, and Andrew K Recknagel, and Gary A Churchill, and Eva M Eicher
Ontogenic and morphological study of gonadal formation in genetically-modified sex reversal XY(POS) mice.
January 2016, The Journal of veterinary medical science,
Gerrit J Bouma, and Kenneth H Albrecht, and Linda L Washburn, and Andrew K Recknagel, and Gary A Churchill, and Eva M Eicher
Evidence to exclude SOX9 as a candidate gene for XY sex reversal without skeletal malformation.
September 1996, Journal of medical genetics,
Gerrit J Bouma, and Kenneth H Albrecht, and Linda L Washburn, and Andrew K Recknagel, and Gary A Churchill, and Eva M Eicher
Live Birth in Sex-Reversed XY Mice Lacking the Nuclear Receptor Dax1.
February 2020, Scientific reports,
Gerrit J Bouma, and Kenneth H Albrecht, and Linda L Washburn, and Andrew K Recknagel, and Gary A Churchill, and Eva M Eicher
nr0b1 (DAX1) mutation in zebrafish causes female-to-male sex reversal through abnormal gonadal proliferation and differentiation.
September 2016, Molecular and cellular endocrinology,
Copied contents to your clipboard!