Phenotypes associated with this allele

• Allele Symbol: Prkaca^tm1Gsm
• Allele Name: targeted mutation 1, G Stanley McKnight
• Allele ID: MGI:2181021
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Prkaca^tm1Gsm/Prkaca^tm1Gsm	involves: 129X1/SvJ * C57BL/6	MGI:2663265
ht2	Prkaca^tm1Gsm/Prkaca^+	involves: 129X1/SvJ * C57BL/6	MGI:4868207
cx3	Prkaca^tm1Gsm/Prkaca^+ Prkar1a^tm1.1Lsk/Prkar1a^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:4868214
cx4	Prkaca^tm1Gsm/Prkaca^tm1Gsm Prkar1a^tm1Gsm/Prkar1a^tm1Gsm	involves: 129X1/SvJ * C57BL/6	MGI:3625132
cx5	Prkaca^tm1Gsm/Prkaca^+ Prkacb^tm1Gsm/Prkacb^tm1Gsm	involves: 129X1/SvJ * C57BL/6	MGI:3628809
cx6	Prkaca^tm1Gsm/Prkaca^tm1Gsm Prkacb^tm1Gsm/Prkacb^+	involves: 129X1/SvJ * C57BL/6	MGI:3628811
cx7	Prkaca^tm1Gsm/Prkaca^tm1Gsm Prkacb^tm1Gsm/Prkacb^tm1Gsm	involves: 129X1/SvJ * C57BL/6	MGI:3628813

Genotype
MGI:2663265

hm1

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

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:77110 )

• influenced by genetic background, with decreased survival associated with increased C57BL/6 contribution

• some mice surviving past weaning

growth/size/body

decreased body weight ( J:77110 )

• 35% reduction in weight at 3 months of age relative to wild-type littermates

postnatal growth retardation ( J:76765 , J:77110 )

• beginning at 2 weeks of age (J:77110)

• normal serum levels of growth hormone (GH) though mice were partially GH resistant (J:77110)

homeostasis/metabolism

decreased urine protein level ( J:77110 )

• reduction in the levels of major urinary proteins

renal/urinary system

decreased urine protein level ( J:77110 )

• reduction in the levels of major urinary proteins

reproductive system

reproductive system phenotype ( J:77110 )

N • full spectrum of male gametes observed indicating normal spermatogenesis

N • normal testicular weight

N • normal sperm count

asthenozoospermia ( J:77110 )

♂ • reduced forward velocity

male infertility ( J:76765 )

♂

cellular

asthenozoospermia ( J:77110 )

♂ • reduced forward velocity

Genotype
MGI:4868207

ht2

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

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

cx3

• 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:3625132

cx4

• Allelic Composition: Prkaca^tm1Gsm/Prkaca^tm1Gsm; Prkar1a^tm1Gsm/Prkar1a^tm1Gsm
• Genetic Background: involves: 129X1/SvJ * C57BL/6

cardiovascular system

pericardial edema ( J:78010 )

• E10.5 embryos exhibit an expanded fluid-filled pericardial cavity, even though exhibit rescue of the other phenotypes seen in Prkar1a null mice (develop a heart tube, undergo embryo turning, etc)

homeostasis/metabolism

pericardial edema ( J:78010 )

• E10.5 embryos exhibit an expanded fluid-filled pericardial cavity, even though exhibit rescue of the other phenotypes seen in Prkar1a null mice (develop a heart tube, undergo embryo turning, etc)

Genotype
MGI:3628809

cx5

• 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

Genotype
MGI:3628811

cx6

• Allelic Composition: Prkaca^tm1Gsm/Prkaca^tm1Gsm; Prkacb^tm1Gsm/Prkacb⁺
• 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

embryonic lethality, complete penetrance ( J:76765 )

• die by E14

nervous system

abnormal neural tube morphology ( J:76765 )

• 75% show spinal neural tube defects

• 25% show spinal neural tube defects and exencephaly

• 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

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

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

exencephaly ( J:76765 )

• 25% show spinal neural tube defects and exencephaly; exencephaly alone is not observed

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 )

• 75% show spinal neural tube defects

• 25% show spinal neural tube defects and exencephaly

• 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

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

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

Genotype
MGI:3628813

cx7

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

mortality/aging

embryonic lethality between somite formation and embryo turning, complete penetrance ( J:76765 )

• all double mutants found at E8.5 to E10.5 are in various stages of resorption, indicating early embryonic lethality