Phenotypes for Nr3c1 MGI:3762956 MGI Mouse

neonatal lethality, incomplete penetrance ( J:27441 )

• Background Sensitivity: on a mixed genetic background, most homozygous mice die shortly after birth with a few (4.5%) survivors present at 4 weeks of age; on a 129 isogenic background, all homozygous mice die at birth

abnormal adrenal gland morphology ( J:27441 )

• overall, adrenals appear disorganized

• normal formation of the zona glomerulosa

abnormal adrenal cortex morphology ( J:27441 )

• the expression of steroid biosynthetic enzymes is elevated 2-3 fold or more

increased adrenal gland zona fasciculata size ( J:27441 )

• hypertrophy, with increased production of corticosterone

abnormal adrenal gland zona reticularis morphology ( J:27441 )

• hypertrophy, with increased production of corticosterone

enlarged adrenocortical cells ( J:27441 )

• prominent hypertrophy and possible hyperplasia of adrenal cortical cells, apparent by day 15 p.c.

• cells are enlarged 2-3 fold

enlarged adrenocortical cell nuclei ( J:27441 )

abnormal adrenal chromaffin cell morphology ( J:27441 )

• at E18.5, a small number of tyrosine hydroxylase (TH)-expressing chromaffin cells are scattered among the enlarged cells of the cortex instead of in the medulla

• these cells do not express phenylethanolamine N-methyltransferase (PNMT) suggesting that these are noradrenergic chromaffin cells

• at E13.5 and E15.5, a greatly reduced number of chromaffin cells are present in adrenal glands in mutant embryos

absent adrenergic chromaffin cells ( J:27441 )

• among the scattered chromaffin cells present in the cortex, these do not express phenylethanolamine N-methyltransferase (PNMT) suggesting that these are noradrenergic chromaffin cells and that adrenergic cells are missing

• only noradrenaline-specific chromaffin granules are present in chromaffin cells

absent adrenal medulla ( J:27441 )

• no central medulla of chromaffin cells is present in mice at E18.5

• in surviving adults, the medullary region is replaced by a mass of white adipose and loose, highly vascularized connective tissue

enlarged adrenal glands ( J:27441 )

• adrenal glands are approximately twice the size of controls

increased circulating corticosterone level ( J:27441 )

• total plasma level is increased 2-3 fold

increased circulating adrenocorticotropin level ( J:27441 )

• total plasma levels are increased more than 20 fold

cyanosis ( J:27441 )

• at E18.5, mice appear cyanotic

decreased adrenaline level ( J:27441 )

• mutant adrenal glands contain no adrenaline

decreased noradrenaline level ( J:27441 )

• mutant adrenals contain a reduced amount of noradrenaline

atelectasis ( J:27441 )

• severe at birth, with little or no inflation of the lungs in dying animals

abnormal respiratory system development ( J:27441 )

• despite defects in branching morphogenesis of the bronchioles and alveoli, expression of surfactant protein genes in the developing respiratory epithelium and in the developing lung is similar to controls

• the number of type II alveolar cells is similar to controls

abnormal lung development ( J:27441 )

• a reduction in the level of expression of amiloride-sensitive Na+ channel mRNA is seen; this may account for a reduction in sodium transport and water removal from the lungs before birth

abnormal branching involved in terminal bronchiole morphogenesis ( J:27441 )

• impaired development of terminal bronchioles

impaired lung alveolus development ( J:27441 )

• impaired development of alveoli

respiratory distress ( J:27441 )

• at birth, homozygous mice exhibit respiratory distress

abnormal liver physiology ( J:27441 )

• at birth, a reduction in the activation of gluconeogenic enzymes is seen, including G6pc (glucose-6-phosphatase), Tat (tyrosine aminotransferase) and Sds (serine dehydratase)