Phenotypes associated with this allele

• Allele Symbol: Prkaca⁺
• Allele Name: wild type
• Allele ID: MGI:2431708
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Prkaca^tm1Gsm/Prkaca^+	involves: 129X1/SvJ * C57BL/6	MGI:4868207
cx2	Prkaca^tm1Gsm/Prkaca^+ Prkar1a^tm1.1Lsk/Prkar1a^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:4868214
cx3	Prkaca^tm1Gsm/Prkaca^+ Prkacb^tm1Gsm/Prkacb^tm1Gsm	involves: 129X1/SvJ * C57BL/6	MGI:3628809

Genotype
MGI:4868207

ht1

• Allelic Composition: Prkaca^tm1Gsm/Prkaca⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6

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

skeleton

decreased trabecular bone thickness ( J:160299 )

• trabecular bone is decreased

abnormal skeleton development ( J:160299 )

• mutants exhibit overall gain in bone formation derived from primarily cortical bone

Genotype
MGI:4868214

cx2

• 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

Genotype
MGI:3628809

cx3

• Allelic Composition: Prkaca^tm1Gsm/Prkaca⁺; Prkacb^tm1Gsm/Prkacb^tm1Gsm
• Genetic Background: involves: 129X1/SvJ * C57BL/6

Neural tube defects leading to spina bifida in Prkaca^tm1Gsm/Prkaca⁺ Prkacb^tm1Gsm/Prkacb^tm1Gsm and Prkaca^tm1Gsm/Prkaca^tm1Gsm Prkacb^tm1Gsm/Prkacb⁺ mice

mortality/aging

postnatal lethality ( J:76765 )

• if mutant pups are kept with their parents, they are rejected and left out of the litter and die, probably from starvation

nervous system

increased neural tube apoptosis ( J:76765 )

• increase in apoptotic cells in the dorsal and lateral regions of the neural tube

abnormal neural tube morphology ( J:76765 )

• 100% show spinal neural tube defects

• E9.5-10.5 embryos exhibit a closed neural tube with an expanded alar plate and enlarged lumen in the thoracic and lumbar regions and an expanded neuroepithelium

• E10.5 or older embryos show a drastic increase in the expansion of the neural canal (enlarged lumen) and a neuroepithelium with a higher cell density

abnormal embryonic neuroepithelium morphology ( J:76765 )

• E9.5-E10.5 embryos exhibit an expanded neuroepithelium with a higher cell density

spina bifida ( J:76765 )

• at the thoracic and lumbar regions

abnormal neuron specification ( J:76765 )

• altered neuronal identity in the neural tube posterior to the forelimb buds leading to a ventralized neural tube (appearance of ventral neuronal progenitors in the dorsal neural tube and loss of dorsal cell types)

abnormal dorsal root ganglion morphology ( J:76765 )

• dorsal root ganglia form in E10.5 embryos but regress at E12.5

• significant increase in cell death in the dorsal root ganglia adjacent to the affected neural tube

disorganized dorsal root ganglion ( J:76765 )

• dorsal root ganglia are formed in E10.5 embryos but are disorganized

skeleton

abnormal vertebral column morphology ( J:76765 )

• spinal column defects are located in the thoracic and lumbar regions

abnormal spine curvature ( J:76765 )

• ventral curvature of the spine at the defective region

abnormal vertebral arch morphology ( J:76765 )

• vertebral arches fail to fuse at the dorsal midline between forelimbs and hindlimbs

embryo

abnormal neural tube morphology ( J:76765 )

• 100% show spinal neural tube defects

• E9.5-10.5 embryos exhibit a closed neural tube with an expanded alar plate and enlarged lumen in the thoracic and lumbar regions and an expanded neuroepithelium

• E10.5 or older embryos show a drastic increase in the expansion of the neural canal (enlarged lumen) and a neuroepithelium with a higher cell density

abnormal embryonic neuroepithelium morphology ( J:76765 )

• E9.5-E10.5 embryos exhibit an expanded neuroepithelium with a higher cell density

spina bifida ( J:76765 )

• at the thoracic and lumbar regions

cellular

increased neural tube apoptosis ( J:76765 )

• increase in apoptotic cells in the dorsal and lateral regions of the neural tube