International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


ORAL PRESENTATION

TUESDAY 11 NOVEMBER
09:45 – 10:00 HRS

GENETIC CONTROL OF ADRENAL DEVELOPMENT AND FUNCTION: INTERACTION OF DAX1 AND STEROIDOGENIC FACTOR-1

Keegan C
University of Michigan

Co-Authors: 1) Shah S, 2) Jameson L, 1) Hammer G
Institutions: 1) University of Michigan, 2) Northwestern University

The adrenal cortex is critical for homeostasis and stress response. Composed of three functionally distinct zones, it is an excellent model for the study of organogenesis, stem cell renewal, and cell lineage. In humans, the transient fetal zone forms in utero and regresses after birth. In mice, the homologous X-zone (XZ) forms after birth and regresses at puberty in males and during pregnancy in females. Thus, the mouse is an invaluable tool for studying human adrenocortical development. Steroidogenic Factor-1 (SF-1) and DAX1 are nuclear receptors that are essential for adrenocortical and gonadal function in both species. Human mutations in SF-1 cause adrenal insufficiency and sex reversal, while DAX1 mutations cause adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism. Sf1 knockout mice lack adrenals and gonads, while Dax1 null mice have normal adrenocortical function but retain the XZ. Both genes exhibit dosage sensitivity. Sf1 haploinsufficient mice exhibit smaller adrenal glands and impaired steroidogenesis. Dax1 deficiency rescues the adrenocortical defects in adult Sf1 haploinsufficient mice; thus, DAX1 functions as a repressor of SF-1 action in the adrenal. A similar model is emerging in the gonad, reflecting its similar embryonic origin. We report an opposing interaction between SF-1 and DAX1 during adrenocortical XZ formation and regression. Histologic analyses in genetically modified mice reveal a critical role for SF-1 in XZ regression and DAX1 in XZ growth maintenance. Additional studies using these and other mouse models of aberrant adrenocortical development will lead to a better understanding human AHC and adrenocortical cancer.


Abstracts * Officers * Bylaws * Application Form * Meeting Calendar * Contact Information * Home * Resources * News and Views * Membership

Base url http://imgs.org
Last modified: Saturday, November 3, 2012