Phenotypes Associated with This Genotype

Genotype
MGI:5897214

• Allelic Composition: Tg(CMV-tTA)3Bjd/0; Tg(tetO-Prkar1a*x2as)1Stra/0
• Genetic Background: involves: C57BL/6 * NMRI * SJL

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

mortality/aging

premature death ( J:94953 )

• mice show decreased survival after 16 months of age, with most dying of metastatic lymphomas, histiocytic sarcomas or other proliferative disorders

growth/size/body

thyroid gland cyst ( J:95465 )

• 40% of mice develop thyroid follicular hyperplasia, adenomas, and cysts

decreased body weight ( J:95465 )

• mice weigh less than controls up to 4 weeks of age but later show no weight differences until 6 months of age when they start to gain weight

inguinal hernia ( J:95465 )

• inguinal hernias due to accumulation of lower abdominal visceral fat

increased susceptibility to weight gain ( J:95465 )

• mice continue to gain weight after 6 months of age and become heavier than controls by 14 months of age

adipose tissue

abnormal adipose tissue morphology ( J:95465 )

• weight gain is largely due to accumulation of lower abdominal visceral fat

neoplasm

increased thyroid adenoma incidence ( J:94953 , J:95465 )

• thyroid follicular adenoma (J:94953)

• 40% of mice develop thyroid follicular hyperplasia, adenomas, and cysts (J:95465)

increased liver tumor incidence ( J:94953 )

• 4 of 44 mice develop liver tumors which include histiocytic sarcoma, hepatocellular adenoma, and round cell neoplasia

increased liver adenoma incidence ( J:94953 )

increased metastatic potential ( J:94953 )

• 8 of 44 mice develop metastatic tumors which include spindle cell tumor, round cell tumor, squamous cell papilloma, and/or lymphoma

increased lymphoma incidence ( J:94953 )

• lymphomas develop in primary lymphoid organs (thymus, spleen, lymph nodes, Peyers patches) and other tissues (liver and kidney)

increased histiocytic sarcoma incidence ( J:94953 )

increased spindle cell carcinoma incidence ( J:94953 )

increased papilloma incidence ( J:94953 )

• squamous cell papilloma

increased skin papilloma incidence ( J:95465 )

• skin squamous cell papilloma

increased Schwannoma incidence ( J:95465 )

• spindle cell, schwannomatous tumor

endocrine/exocrine glands

abnormal adrenal gland morphology ( J:94953 )

• 14 of 26 mice exhibit adrenal gland congestion, hyperplasia and/or X-zone hypertrophy

abnormal adrenal cortex morphology ( J:95465 )

• mice develop adrenocortical abnormalities

• adrenal glands exhibit extra-epithelial pigment cells containing melanosomes that are in direct cellular contact with adrenocortical cells

• adrenal cortex exhibits congestion

abnormal adrenal gland x-zone morphology ( J:94953 , J:95465 )

• X-zone hypertrophy (J:94953)

• X zone hyperplasia is seen after puberty in males or after multiple pregnancies in females (J:95465)

retention of the adrenal gland x-zone ( J:95465 )

• X zone persistence is seen after puberty in males or after multiple pregnancies in females

abnormal adrenocortical cell morphology ( J:95465 )

• adrenocortical cells show cytoplasm with ample smooth endoplasmic reticulum, an increased number of round mitochondria with tubulovesicular internal membranes that bridge the mitochondrial matrix, and reduced number of cholesterol storing liposomes

• adrenocortical cells have frequent and large pigment deposits and often other, vesicle-like structures

adrenal cortical hyperplasia ( J:95465 )

• cortical hyperplasia with pigment deposits and congestion are seen more frequently than in controls

adrenal gland hyperplasia ( J:94953 )

abnormal thyroid follicle morphology ( J:94953 , J:95465 )

• 12 of 30 mice exhibit thyroid follicular lesions, including follicular adenoma, follicular hyperplasia or ectasia, and colloid goiter (J:94953)

• 40% of mice develop thyroid follicular hyperplasia, adenomas, and cysts (J:95465)

thyroid gland hyperplasia ( J:94953 )

• follicular hyperplasia of the thyroid and/or colloid goiter

thyroid gland cyst ( J:95465 )

• 40% of mice develop thyroid follicular hyperplasia, adenomas, and cysts

increased thyroid adenoma incidence ( J:94953 , J:95465 )

• thyroid follicular adenoma (J:94953)

• 40% of mice develop thyroid follicular hyperplasia, adenomas, and cysts (J:95465)

pancreas inflammation ( J:94953 )

• 6 of 29 mice develop pancreatic inflammation or lymphoid infiltrate into the pancreas

homeostasis/metabolism

increased circulating corticosterone level ( J:95465 )

• mice exhibit higher corticosterone levels before, during and after administration of dexamethasone

integument

increased skin papilloma incidence ( J:95465 )

• skin squamous cell papilloma

immune system

pancreas inflammation ( J:94953 )

• 6 of 29 mice develop pancreatic inflammation or lymphoid infiltrate into the pancreas

abnormal lymph node morphology ( J:94953 )

• 15 of 33 mice show lymph node histiocytic hyperplasia

nervous system

increased Schwannoma incidence ( J:95465 )

• spindle cell, schwannomatous tumor

liver/biliary system

increased liver tumor incidence ( J:94953 )

• 4 of 44 mice develop liver tumors which include histiocytic sarcoma, hepatocellular adenoma, and round cell neoplasia

increased liver adenoma incidence ( J:94953 )

cellular

retention of the adrenal gland x-zone ( J:95465 )

• X zone persistence is seen after puberty in males or after multiple pregnancies in females

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Carney complex		DOID:0050471	OMIM:160980 OMIM:605244 OMIM:608837	J:95465
primary pigmented nodular adrenocortical disease		DOID:0060280	OMIM:610475 OMIM:610489 OMIM:614190 OMIM:615830	J:95465