Homeostatic responses in the adrenal cortex to the absence of aldosterone in mice.
To study the effects of decreased amounts or absence of aldosterone on development and endocrine function, we have disrupted the mouse gene, Cyp11b2, coding for aldosterone synthase (AS) by replacing its first two exons with sequences coding for enhanced green fluorescent protein. The null pups fail to thrive postnatally, and about 30% die between d 7 and 28. Aldosterone in plasma and AS mRNA in adrenal glands are undetectable in the null mice. Adult AS-null mice are small, weigh 75% of wild type, are hypotensive, have increased concentrations of plasma K(+) and corticosterone, and a decreased concentration of plasma Cl(-). Their plasma renin and angiotensin II concentrations are 45x and 4x wild type. The adrenal cortex is disorganized and has cells that contain marked accumulations of lipid. The zona glomerulosa is widened and includes easily detectable renin-containing cells, not seen in the wild-type adrenal gland. In the AS-/- adrenals, the level of mRNA for Cyp11b1, coding for 11beta-hydroxylase, is 150% wild type. The adrenal glands of the null mice consequently show evidence of a greatly activated renin-angiotensin system and up-regulation of glucocorticoid production. In the AS-null mice enhanced green fluorescent protein fluorescence is mainly at the boundary between the cortex and medulla, where apoptotic cells are numerous. These data are consistent with the absence of aldosterone in the AS-null mice inducing an increased cell-turnover of cells in the adrenals that normally become AS expressing and their migration to the medullary boundary where they apoptose.
Lee
Gene
G
Department of Pathology and Laboratory Medicine, University of North Carolina, 703 Brinkhous-Bullitt Building, Chapel Hill, North Carolina 27599-7525, USA.
Makhanova
Natalia
N
Caron
Kathleen
K
Lopez
Maria L Sequeira
ML
Gomez
R Ariel
RA
Smithies
Oliver
O
Kim
Hyung-Suk
HS
D000302:Adrenal Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D002712:Chlorides / Q000097:blood; D003345:Corticosterone / Q000097:blood; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006706:Homeostasis / Q000502:physiology*; D007022:Hypotension / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009929:Organ Size; D010641:Phenotype; D011188:Potassium / Q000097:blood; D012083:Renin / Q000378:metabolism
D002712:Chlorides; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D012083:Renin; D011188:Potassium; D003345:Corticosterone