Phenotypes associated with this allele

• Allele Symbol: Prkar1a^tm1Gsm
• Allele Name: targeted mutation 1, G Stanley McKnight
• Allele ID: MGI:2183602
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Prkar1a^tm1Gsm/Prkar1a^tm1Gsm	involves: 129X1/SvJ * C57BL/6	MGI:3625127
ht2	Prkar1a^tm1Gsm/Prkar1a^+	involves: 129X1/SvJ	MGI:3625140
cx3	Prkaca^tm1Gsm/Prkaca^tm1Gsm Prkar1a^tm1Gsm/Prkar1a^tm1Gsm	involves: 129X1/SvJ * C57BL/6	MGI:3625132

Genotype
MGI:3625127

hm1

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

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

Prkar1a^tm1Gsm/Prkar1a^tm1Gsm embryos are severely growth-retarded

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:78010 )

• die between E10.5 and E11.5

growth/size/body

embryonic growth retardation ( J:78010 )

• severe growth retardation with developmental delay

• the E9.5 mutant embryo is similar in size to an E8 wild-type embryo

abnormal embryo size ( J:78010 )

• greatly reduced trunk structure, however anterior-posterior axis is clearly apparent

decreased embryo size ( J:78010 )

• smaller by E7.5

cardiovascular system

abnormal cardiogenic plate morphology ( J:78010 )

• the cardiogenic plate, rather than being displaced more caudally by the formation of the heart tube, it is tightly juxtaposed to the proencephalon

absent heart tube ( J:78010 )

• heart tube does not form although a cardiogenic plate is present

embryo

abnormal developmental patterning ( J:78010 )

failure of initiation of embryo turning ( J:78010 )

• do not initiate the embryo turning process that occurs at the 7-8 somite transition

embryonic growth retardation ( J:78010 )

• severe growth retardation with developmental delay

• the E9.5 mutant embryo is similar in size to an E8 wild-type embryo

abnormal embryo size ( J:78010 )

• greatly reduced trunk structure, however anterior-posterior axis is clearly apparent

decreased embryo size ( J:78010 )

• smaller by E7.5

abnormal embryonic tissue morphology ( J:78010 )

• mutant embryos have a flattened morphology by E7.5

decreased axial mesoderm size ( J:78010 )

• axial mesoderm is greatly reduced in size

decreased paraxial mesoderm size ( J:78010 )

• paraxial mesoderm is greatly reduced in size

abnormal primitive streak morphology ( J:78010 )

• reduction in primitive streak mesoderm

• exhibit aberrant and highly disorganized migration of mesodermal cells away from the primitive streak

• about 1/3 the number of mesodermal cells exit the streak and move laterally and anteriorly, resulting in an accumulation of presumptive mesoderm beneath the primitive streak

abnormal somite shape ( J:78010 )

• somites are irregularly shaped at E9.5

decreased somite size ( J:78010 )

• somites are very small at E9.5

excessive folding of visceral yolk sac ( J:78010 )

• exhibit a ruffled yolk sac membrane by E7.5

cellular

abnormal cell morphology ( J:78010 )

• mesodermal primary embryonic fibroblasts from E8.5 embryos have a flattened and box-shaped or rounded morphology with multiple actin organizing centers that extend in all directions rather than the typical spindled morphology with sparse parallel actin fibers

homeostasis/metabolism

enhanced wound healing ( J:78010 )

• mesodermal primary embryonic fibroblasts complete wound healing faster than wild-type fibroblasts

digestive/alimentary system

abnormal foregut morphology ( J:78010 )

• absence of a heart tube leads to a more radical angle of entry of the foregut

Genotype
MGI:3625140

ht2

• Allelic Composition: Prkar1a^tm1Gsm/Prkar1a⁺
• Genetic Background: involves: 129X1/SvJ

Tumors in Prkar1a^tm1Gsm/Prkar1a⁺ mice

cardiovascular system

decreased heart rate variability ( J:93393 )

• depressed heart rate variability, however exhibit no heart rate changes, conduction delay or any cardiac myxomas

liver/biliary system

increased hepatocellular carcinoma incidence ( J:93393 )

• 5 of 12 mutants that develop tumors have hepatocellular carcinomas

reproductive system

reduced male fertility ( J:93393 )

♂

neoplasm

increased tumor incidence ( J:93393 )

• increase in frequency of extracardiac tumors; 12 of 17 mutants developed tumors

increased hepatocellular carcinoma incidence ( J:93393 )

• 5 of 12 mutants that develop tumors have hepatocellular carcinomas

increased sarcoma incidence ( J:93393 )

• 3 of 12 mutants that develop tumors have soft tissue sarcomas with myxomatous differentiation invading the calvaria

• 2 of 12 mutants that develop tumors have paraspinal and spinal sarcomas (chondro- and meningeal saracomas) with cord compression and lower limb paralysis

increased fibrosarcoma incidence ( J:93393 )

• 2 of 12 mutants that develop tumors have s.c. soft tissue myxoid fibrosarcomas of the forelimb

increased hemangiosarcoma incidence ( J:93393 )

• 4 of 12 mutants that develop tumors have hemangiosarcomas of the spleen with myxoid regions

• splenic hemangiosarcomas are associated with metachronous lesions including colonic, ovarian, and pulmonary hemangiosarcomas

pigmentation

pigmentation phenotype ( J:93393 )

N • pigmentation is normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Carney complex		DOID:0050471	OMIM:160980 OMIM:605244 OMIM:608837	J:93393

Genotype
MGI:3625132

cx3

• 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)