Phenotypes associated with this allele

• Allele Symbol: Prkar1a^tm1.1Lsk
• Allele Name: targeted mutation 1.1, Lawrence S Kirschner
• Allele ID: MGI:3580100
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Prkar1a^tm1.1Lsk/Prkar1a^tm1.1Lsk	involves: 129S1/Sv * 129X1/SvJ	MGI:3580531
ht2	Prkar1a^tm1.1Lsk/Prkar1a^+	either: (involves: 129S1/Sv * 129X1/SvJ * C3H) or (involves: 129S1/Sv * 129X1/SvJ * A/J)	MGI:3580532
ht3	Prkar1a^tm1.1Lsk/Prkar1a^+	involves: 129S1/Sv * 129X1/SvJ	MGI:3580533
ht4	Prkar1a^tm1.1Lsk/Prkar1a^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:4868217
cx5	Prkaca^tm1Gsm/Prkaca^+ Prkar1a^tm1.1Lsk/Prkar1a^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:4868214

Genotype
MGI:3580531

hm1

• Allelic Composition: Prkar1a^tm1.1Lsk/Prkar1a^tm1.1Lsk
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:98799 )

• all homozygotes show advanced stages of tissue breakdown by E9.5

Genotype
MGI:3580532

ht2

• Allelic Composition: Prkar1a^tm1.1Lsk/Prkar1a⁺
• Genetic Background: either: (involves: 129S1/Sv * 129X1/SvJ * C3H) or (involves: 129S1/Sv * 129X1/SvJ * A/J)

reproductive system

infertility ( J:98799 )

• after 3 to 4 generations of inbreeding to C3H or to A/J

Genotype
MGI:3580533

ht3

• Allelic Composition: Prkar1a^tm1.1Lsk/Prkar1a⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

neoplasm

increased tumor incidence ( J:98799 )

• commonly found on proximal hind limb but elsewhere as well

• interlacing bundles of parallel spindle cells with large eosinophilic cytoplasmic granules

• look like hypertrophic Schwann cells - Schwannomas

• no melanotic pigmentation

• tail tumors as well starting around 5 to 6 months

• bone loss in individual vertebrae of the tail

increased thyroid tumor incidence ( J:98799 )

• epithelial thyroid cancer

endocrine/exocrine glands

increased thyroid tumor incidence ( J:98799 )

• epithelial thyroid cancer

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Carney complex		DOID:0050471	OMIM:160980 OMIM:605244 OMIM:608837	J:98799

Genotype
MGI:4868217

ht4

• Allelic Composition: Prkar1a^tm1.1Lsk/Prkar1a⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

skeleton

increased skeletal tumor incidence ( J:160299 )

• heterozygotes develop bone lesions derived from camp-responsive osteogenic cells and resemble fibrous dysplasia

• about 50% of mutants develop osteomyoxomas in the caudal vertebrae by 8 months of age, with 100% of mice showing these by one year

increased osteosarcoma incidence ( J:160299 )

• rare development of metastatic osteochondrosarcomas

decreased bone mineral density ( J:160299 )

abnormal bone mineralization ( J:160299 )

• overall bone mineralization density is lower than in wild-type mice

neoplasm

increased thyroid tumor incidence ( J:160299 )

increased Schwannoma incidence ( J:160299 )

increased skeletal tumor incidence ( J:160299 )

• heterozygotes develop bone lesions derived from camp-responsive osteogenic cells and resemble fibrous dysplasia

• about 50% of mutants develop osteomyoxomas in the caudal vertebrae by 8 months of age, with 100% of mice showing these by one year

increased osteosarcoma incidence ( J:160299 )

• rare development of metastatic osteochondrosarcomas

endocrine/exocrine glands

increased thyroid tumor incidence ( J:160299 )

nervous system

increased Schwannoma incidence ( J:160299 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Carney complex		DOID:0050471	OMIM:160980 OMIM:605244 OMIM:608837	J:160299

Genotype
MGI:4868214

cx5

• Allelic Composition: Prkaca^tm1Gsm/Prkaca⁺; Prkar1a^tm1.1Lsk/Prkar1a⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

neoplasm

neoplasm ( J:160299 )

N • mutants do not develop schwannomas or thyroid tumors

increased skeletal tumor incidence ( J:160299 , J:166728 )

• mutants develop a greater number of osseous lesions and develop them earlier than single Prkar1a heterozygotes (J:160299)

• 90% of mutants exhibit bone lesions in the tail by 6 months and 100% by 9 months of age (J:160299)

• osseous lesions are seen starting around 3 months of age and vary from rare chondromas in the long bones and ubiquitous osteochondrodysplasia of vertebral bodies to occasional sarcoma (J:160299)

• 13% of mutants develop osteochondromyoxoma (J:160299)

• cells from the bone lesions originate from an area proximal to the growth plate (J:160299)

• cartilaginous metaplasia, chondromas, and osteochondrodysplasia are seen in marrow cavities of up to 1/3 of the long bones and most of the vertebral bodies (J:160299)

• lesions are hypercellular and contain more irregular cartilage or bone islands; proliferating cells are committed osteogenic but are not able to mature into osteoblasts (J:160299)

• mutants develop bone tumors with histological resemblance to those seen in humans with neonatal-onset multisystem inflammatory disease, with lesions derived from osteoblast progenitor cells (J:166728)

increased osteosarcoma incidence ( J:160299 )

• rare development of metastatic osteochondrosarcomas

increased osteochondroma incidence ( J:160299 )

• rare chondromas in the long bones

skeleton

increased skeletal tumor incidence ( J:160299 , J:166728 )

• mutants develop a greater number of osseous lesions and develop them earlier than single Prkar1a heterozygotes (J:160299)

• 90% of mutants exhibit bone lesions in the tail by 6 months and 100% by 9 months of age (J:160299)

• osseous lesions are seen starting around 3 months of age and vary from rare chondromas in the long bones and ubiquitous osteochondrodysplasia of vertebral bodies to occasional sarcoma (J:160299)

• 13% of mutants develop osteochondromyoxoma (J:160299)

• cells from the bone lesions originate from an area proximal to the growth plate (J:160299)

• cartilaginous metaplasia, chondromas, and osteochondrodysplasia are seen in marrow cavities of up to 1/3 of the long bones and most of the vertebral bodies (J:160299)

• lesions are hypercellular and contain more irregular cartilage or bone islands; proliferating cells are committed osteogenic but are not able to mature into osteoblasts (J:160299)

• mutants develop bone tumors with histological resemblance to those seen in humans with neonatal-onset multisystem inflammatory disease, with lesions derived from osteoblast progenitor cells (J:166728)

increased osteosarcoma incidence ( J:160299 )

• rare development of metastatic osteochondrosarcomas

increased osteochondroma incidence ( J:160299 )

• rare chondromas in the long bones

decreased bone mineral density ( J:160299 )

• overall bone mineralization density is lower than in wild-type mice

abnormal compact bone morphology ( J:160299 )

• in affected bones, normal cortical bone is replaced by mineralized material

abnormal periosteum morphology ( J:160299 )

• periosteum of affected bones is abnormal, with occasional cells from lesions crossing the periosteum into the extraosseous space and Sharpey fibers, characteristic of fibrous dysplasia, are observed

abnormal bone mineralization ( J:160299 )

• although the bone marrow is expanded by active osteoclastic activity, these cells are not able to mature into osteoblasts and mineralize the matrix resulting in undermineralization

• bones exhibit a lag between bone matrix formation and mineralization and abnormal coordination of these processes with bone resorption

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
CINCA Syndrome		DOID:0090029	OMIM:607115	J:166728