Phenotypes Associated with This Genotype

Genotype
MGI:4819186

• Allelic Composition: Prkar1a^tm1Lsk/Prkar1a^tm1Lsk; Tg(Akr1b7-cre)1Anm/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2

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

Morphological defects and progressive hyperplasia in Prkar1a^tm1Lsk/Prkar1a^tm1Lsk Tg(Akr1b7-cre)1Anm/0 adrenals

cellular

increased adrenal gland apoptosis ( J:161521 )

• at 5 and 10 months, mice exhibit increased apoptosis in the adrenal gland compared with wild-type mice

retention of the adrenal gland x-zone ( J:161521 )

• at 18 months, female mice exhibit an expanded X-like-zone and replaces most of the cortex compared with wild-type mice

endocrine/exocrine glands

abnormal adrenal cortex morphology ( J:161521 )

• eosinophilic fetal cells occupy 50% of the cortex at 10 months and most of the cortex by 18 months unlike in wild-type mice

retention of the adrenal gland x-zone ( J:161521 )

• at 18 months, female mice exhibit an expanded X-like-zone and replaces most of the cortex compared with wild-type mice

decreased adrenal gland zona fasciculata size ( J:161521 )

• atrophic at 18 months

disorganized adrenal gland zona fasciculata ( J:161521 )

• disorganized by 10 months

abnormal adrenal gland zona glomerulosa morphology ( J:161521 )

• groups of glomeruli are isolated from each other by small hyperplastic spindle-shaped basophilic cells unlike in wild-type mice

adrenal cortical hyperplasia ( J:161521 )

• with emergence of large eosinophilic fetal cells in the innermost part of the adrenal cortex at 5 months

abnormal adrenal gland physiology ( J:161521 )

• at 18 months, the number of proliferative cells in the adrenal cortex is doubled compared to in wild-type mice

• however, cell proliferation at 5 and 10 months is normal

increased adrenal gland apoptosis ( J:161521 )

• at 5 and 10 months, mice exhibit increased apoptosis in the adrenal gland compared with wild-type mice

homeostasis/metabolism

increased circulating corticosterone level ( J:161521 )

• at 10 and 18 months, female mice at least 2-fold in plasma corticosterone level without an increase in ACTH compared with wild-type mice

• following treatment with dexamethasone and ACTH, female mice exhibit an increase in plasma corticosterone level compared with similarly treated wild-type mice

• gonadectomized male mice exhibit an increase in corticosterone levels unlike similarly treated wild-type mice

decreased physiological sensitivity to xenobiotic ( J:161521 )

• following dexamethasone treatment, female mice fail to exhibit reduced adrenal gland weight, cortical atrophy, or reduced corticosterone levels unlike similarly treated wild-type mice

adipose tissue

abnormal adipose tissue distribution ( J:161521 )

• at 10 months, female mice have an accumulation of adipose tissue on the neck (buffalo hump) unlike wild-type mice

• however, male mice do not develop buffalo humps

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
primary pigmented nodular adrenocortical disease		DOID:0060280	OMIM:610475 OMIM:610489 OMIM:614190 OMIM:615830	J:161521