Phenotypes associated with this allele

• Allele Symbol: Nr3c1^tm1Gsc
• Allele Name: targeted mutation 1, Gunther Schutz
• Allele ID: MGI:1857745
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc	involves: 129P2/OlaHsd	MGI:3778619
hm2	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc	involves: 129P2/OlaHsd * 129/Sv	MGI:4887401
hm3	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc	involves: 129P2/OlaHsd * C57BL/6	MGI:3762956

Genotype
MGI:3778619

hm1

• Allelic Composition: Nr3c1^tm1Gsc/Nr3c1^tm1Gsc
• Genetic Background: involves: 129P2/OlaHsd

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

decreased survivor rate ( J:54931 , J:81588 )

• 20% of mice survive perinatal lethality (J:54931)

• 20% survive to adulthood with no respiratory distress and full fertility (J:81588)

neonatal lethality, incomplete penetrance ( J:81588 )

• 80% die shortly after birth of respiratory failure

perinatal lethality, incomplete penetrance ( J:54931 )

• most mice die at birth

• however, 20% of mice survive

endocrine/exocrine glands

abnormal adrenal chromaffin cell morphology ( J:54931 )

• adrenal chromaffin cells exhibit reduced TH, PNMT and chromogranin B immunoreactivity compared to in wild-type mice

• adrenal chromaffin cells fail to express sympathetic neuronal markers unlike in wild-type mice

• chromaffin cells exhibit reduced volume density and diameter of granules at E 14.5 and E16.5 compared to wild-type cells

• however, the number of chromaffin cells are normal and NGF-stimulated adrenal chromaffin cells extend neurites normally

homeostasis/metabolism

absent circulating adrenaline ( J:54931 )

decreased circulating noradrenaline level ( J:54931 )

respiratory system

respiratory failure ( J:81588 )

nervous system

abnormal adrenal chromaffin cell morphology ( J:54931 )

• adrenal chromaffin cells exhibit reduced TH, PNMT and chromogranin B immunoreactivity compared to in wild-type mice

• adrenal chromaffin cells fail to express sympathetic neuronal markers unlike in wild-type mice

• chromaffin cells exhibit reduced volume density and diameter of granules at E 14.5 and E16.5 compared to wild-type cells

• however, the number of chromaffin cells are normal and NGF-stimulated adrenal chromaffin cells extend neurites normally

Genotype
MGI:4887401

hm2

• Allelic Composition: Nr3c1^tm1Gsc/Nr3c1^tm1Gsc
• Genetic Background: involves: 129P2/OlaHsd * 129/Sv

mortality/aging

perinatal lethality, complete penetrance ( J:98065 )

• 100% perinatal death

respiratory system

abnormal lung morphology ( J:98065 )

• at E18.5, mutant lungs display a significantly more condensed tissue morphology than wild-type lungs

increased lung weight ( J:98065 )

• at E18.5, mutant lung wet weight to body weight ratio is significantly increased

pulmonary hyperplasia ( J:98065 )

• at E18.5, lung wet weight and DNA content are significantly higher in mutant lungs, indicating significant hypercellularity

abnormal lung development ( J:98065 )

• mutants display altered development of the terminal respiratory units of the lung

abnormal pulmonary alveolus morphology ( J:98065 )

• at E18.5, mutant lungs lack normal airspace formation

abnormal pulmonary alveolus epithelial cell morphology ( J:98065 )

• at E18.5, mutant lungs display altered alveolar epithelial cell differentiation, primarily causing a reduction in the number of differentiated type I epithelial cells

decreased type I pneumocyte number ( J:98065 )

• at E18.5, the proportions of type-I cells are reduced by ~50%

• a 50% decrease in mRNA levels for T1alpha and aquaporin-5 (two type I cell-specific markers) is observed

increased type II pneumocyte number ( J:98065 )

• at E18.5, the proportions of type II cells are increased by ~30%

abnormal alveolocapillary membrane morphology ( J:98065 )

• at E18.5, mutant lungs show significantly thicker air/blood gas diffusion barriers, with multiple cellular compartments between the airways and adjacent capillaries

• no evidence of epithelial cell and endothelial cell basement membrane fusion is observed

• airway to capillary diffusion distance is increased 6-fold

thick pulmonary interalveolar septum ( J:98065 )

• at E18.5, mutant lungs display thickened interalveolar septa

abnormal surfactant secretion ( J:98065 )

• at E18.5, mRNA levels of type II epithelial cell surfactant protein genes A and C are reduced by ~50%

homeostasis/metabolism

increased circulating corticosterone level ( J:98065 )

• at E18.5, circulating levels of plasma corticosterone are increased by >3-fold relative to those in wild-type controls

growth/size/body

increased lung weight ( J:98065 )

• at E18.5, mutant lung wet weight to body weight ratio is significantly increased

pulmonary hyperplasia ( J:98065 )

• at E18.5, lung wet weight and DNA content are significantly higher in mutant lungs, indicating significant hypercellularity

Genotype
MGI:3762956

hm3

• Allelic Composition: Nr3c1^tm1Gsc/Nr3c1^tm1Gsc
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

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

endocrine/exocrine glands

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

homeostasis/metabolism

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

respiratory system

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

liver/biliary system

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)

nervous system

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