Phenotypes associated with this allele

• Allele Symbol: Rps6kb1^tm1Gtho
• Allele Name: targeted mutation 1, George Thomas
• Allele ID: MGI:2387472
• Summary: 10 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho	B6.129P2-Rps6kb1^tm1Gtho	MGI:3771307
hm2	Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho	involves: 129P2/OlaHsd	MGI:3771312
hm3	Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho	involves: 129P2/OlaHsd * C57BL/6	MGI:3042364
cn4	Pten^tm1Hwu/Pten^tm1Hwu Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho Tg(Mx1-cre)1Cgn/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CBA	MGI:4944270
cx5	Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho Rps6kb2^tm1Gtho/Rps6kb2^tm1Gtho	B6.129P2-Rps6kb1^tm1Gtho Rps6kb2^tm1Gtho	MGI:3771308
cx6	Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho Tg(Ins2-Akt1*)3Mbb/0	B6.Cg-Rps6kb1^tm1Gtho Tg(Ins2-Akt1*)3Mbb	MGI:5829205
cx7	Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho Rps6kb2^tm1Gtho/Rps6kb2^tm1Gtho	involves: 129P2/OlaHsd	MGI:3771311
cx8	Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho Rps6kb2^tm1Gtho/Rps6kb2^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3771310
cx9	Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho Rps6kb2^tm1Gtho/Rps6kb2^tm1Gtho	involves: 129P2/OlaHsd * C57BL/6	MGI:3771309
cx10	Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho Rps6kb2^tm1Gtho/Rps6kb2^tm1Gtho Tg(Ins2-Akt1*)3Mbb/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:5829203

Genotype
MGI:3771307

hm1

• Allelic Composition: Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho
• Genetic Background: B6.129P2-Rps6kb1^tm1Gtho

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

Beta cell and islet size in Tg(Ins2-Akt1*)3Mbb/0, Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho, and double mutant mice

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:144599 )

• pancreatic beta cells are 30% smaller than in wild-type pancreas

decreased pancreatic beta cell mass ( J:144599 )

• beta cell mass is reduced by half

abnormal pancreatic beta cell physiology ( J:144599 )

• beta cell size is not reduced by rapamycin or nutrient starvation as seen in wild-type cells

growth/size/body

decreased body weight ( J:144599 )

postnatal growth retardation ( J:89696 )

• growth retardation is comparable to that observed on a mixed background

homeostasis/metabolism

decreased circulating insulin level ( J:144599 )

• 35% reduction of plasma insulin levels

increased insulin sensitivity ( J:144599 )

Genotype
MGI:3771312

hm2

• Allelic Composition: Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho
• Genetic Background: involves: 129P2/OlaHsd

muscle

decreased skeletal muscle fiber diameter ( J:129852 )

• the reduction in muscle cell diameter observed is comparable to that observed in Rps6kb1^tm1Gtho Rps6kb2^tm1Gtho homozygotes

• however, muscle cell size could be rescued by transfection of a constitutively active AMPK

Genotype
MGI:3042364

hm3

• Allelic Composition: Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

endocrine/exocrine glands

decreased pancreatic beta cell mass ( J:66406 )

• reduced mass of beta cells, 24% smaller, but normal total number of cells

small pancreatic islets ( J:66406 )

• small pancreatic islets resulting in a one-third decrease in endocrine mass

decreased insulin secretion ( J:66406 )

• defect in insulin secretion from beta cells; amount of insulin secreted per cell was reduced, the secretory potential was compromised

growth/size/body

decreased embryo size ( J:89696 )

• at E12.5, mice are 30% smaller than wild-type mice

decreased body size ( J:52107 , J:89696 )

• noticed at 3 weeks of age; also noted in embryonic stages; less significant in adults (J:52107)

• at birth, mice are 15% smaller than wild-type mice (J:89696)

• at 2 months, mice are 20% smaller than wild-type mice (J:89696)

decreased body weight ( J:52107 )

• at birth, animals weighed 20% less; at 15 weeks, animals weighed 15% less

postnatal growth retardation ( J:52107 , J:89696 )

• slow growth was noted up to 5 weeks of age (J:52107)

homeostasis/metabolism

decreased insulin secretion ( J:66406 )

• defect in insulin secretion from beta cells; amount of insulin secreted per cell was reduced, the secretory potential was compromised

hyperglycemia ( J:66406 )

• demonstrated upon glucose challenge

decreased circulating insulin level ( J:66406 )

• 40-50% reduction in serum insulin levels

impaired glucose tolerance ( J:66406 )

• demonstrated upon glucose challenge

embryo

decreased embryo size ( J:89696 )

• at E12.5, mice are 30% smaller than wild-type mice

Genotype
MGI:4944270

cn4

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CBA

hematopoietic system

enlarged thymus ( J:169097 )

• mice injected with pIpC to induce Pten deletion have an enlarged thymus

enlarged spleen ( J:169097 )

• mice injected with pIpC to induce Pten deletion have an enlarged spleen

neoplasm

increased acute lymphoblastic leukemia incidence ( J:169097 )

• mice injected with pIpC to induce Pten deletion, develop myeloproliferative disease and T-cell acute lymphoblastic leukemia, but at a slower rate than in single Pten mutants

mortality/aging

premature death ( J:169097 )

• mean survival time of mice injected with pIpC to induce Pten deletion is 46 days

immune system

enlarged thymus ( J:169097 )

• mice injected with pIpC to induce Pten deletion have an enlarged thymus

enlarged spleen ( J:169097 )

• mice injected with pIpC to induce Pten deletion have an enlarged spleen

endocrine/exocrine glands

enlarged thymus ( J:169097 )

• mice injected with pIpC to induce Pten deletion have an enlarged thymus

growth/size/body

enlarged spleen ( J:169097 )

• mice injected with pIpC to induce Pten deletion have an enlarged spleen

Genotype
MGI:3771308

cx5

• Allelic Composition: Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho; Rps6kb2^tm1Gtho/Rps6kb2^tm1Gtho
• Genetic Background: B6.129P2-Rps6kb1^tm1Gtho Rps6kb2^tm1Gtho

mortality/aging

perinatal lethality, incomplete penetrance ( J:89696 )

• lethality is comparable to that observed on a mixed background

neonatal lethality, incomplete penetrance ( J:89696 )

• lethality is comparable to that observed on a mixed background

postnatal lethality, incomplete penetrance ( J:89696 )

• lethality is comparable to that observed on a mixed background

growth/size/body

postnatal growth retardation ( J:89696 )

• growth retardation is comparable to that observed on a mixed background

Genotype
MGI:5829205

cx6

• Allelic Composition: Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho; Tg(Ins2-Akt1*)3Mbb/0
• Genetic Background: B6.Cg-Rps6kb1^tm1Gtho Tg(Ins2-Akt1*)3Mbb

Beta cell and islet size in Tg(Ins2-Akt1*)3Mbb/0, Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho, and double mutant mice

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:144599 )

• increase in size of pancreatic beta cells

growth/size/body

decreased body weight ( J:144599 )

homeostasis/metabolism

decreased circulating glucose level ( J:144599 )

• decrease in fed and fasting glucose levels

• control of glycemia after injection of glucose is not affected

decreased circulating insulin level ( J:144599 )

• 35% reduction of plasma insulin levels

increased insulin sensitivity ( J:144599 )

• mice are more insulin sensitive than single Tg(Ins2-Akt1*)3Mbb

Genotype
MGI:3771311

cx7

• Allelic Composition: Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho; Rps6kb2^tm1Gtho/Rps6kb2^tm1Gtho
• Genetic Background: involves: 129P2/OlaHsd

muscle

abnormal skeletal muscle morphology ( J:129852 )

• muscle cells are resistant to the growth inhibition triggered by rapamycin or nutrient deprivation

• however, sensitivity to rapamycin and nutrient deprivation could be restored by transfection of a constitutively active AMPK

increased skeletal muscle glycogen level ( J:129852 )

• in the gastrocnemius

decreased skeletal muscle fiber diameter ( J:129852 )

• muscle cell diameter is reduced by 20% compared to wild-type (6.2+/-0.2 um compared to 8.9+/-0.5 um for wild-type cells in culture)

abnormal muscle physiology ( J:129852 )

• ATP levels in muscle cells is reduced 34% and AMP levels are increased 40% compared to in wild-type mice

• mitochondrial enzyme activity of citrate synthase and cytochrome c oxidase in myotubes is increased 50% to 70% compared to wild-type

homeostasis/metabolism

increased fatty acid beta-oxidation ( J:129852 )

• mitochondrial fatty acid beta-oxidation was also augmented in mutant muscle cell cultures, as measured by [3H]-palmitate oxidation

increased skeletal muscle glycogen level ( J:129852 )

• in the gastrocnemius

abnormal lipid level ( J:129852 )

• in the gastrocnemius, the total lipid content is reduced by half compared to in wild-type mice

cellular

abnormal mitochondrial morphology ( J:129852 )

• mitochondrial mass in myotubes and white adipose tissue is increased compared to in wild-type mice

abnormal cellular respiration ( J:129852 )

• ATP-dependent and -independent oxidative capacity is increased in skeletal muscle

increased fatty acid beta-oxidation ( J:129852 )

• mitochondrial fatty acid beta-oxidation was also augmented in mutant muscle cell cultures, as measured by [3H]-palmitate oxidation

Genotype
MGI:3771310

cx8

• Allelic Composition: Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho; Rps6kb2^tm1Gtho/Rps6kb2⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

postnatal lethality, incomplete penetrance ( J:89696 )

• only 65% of expected embryos survive until weaning

Genotype
MGI:3771309

cx9

• Allelic Composition: Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho; Rps6kb2^tm1Gtho/Rps6kb2^tm1Gtho
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

perinatal lethality, incomplete penetrance ( J:89696 )

• one third of mice are born dead without having emerged from their yolk sacs or detached from their placenta

neonatal lethality, incomplete penetrance ( J:89696 )

• half of the mice that are born alive die within hours with signs of cyanosis

• however, mice that survive day 1 usually reach adulthood

postnatal lethality, incomplete penetrance ( J:89696 )

• only 30% of expected embryos survive until weaning

cardiovascular system

abnormal heart morphology ( J:89696 )

• nonviable and cyanotic mice exhibit dilated heart chambers

abnormal blood circulation ( J:89696 )

• nonviable and cyanotic mice exhibit hyperemia of internal organs

hemorrhage ( J:89696 )

• nonviable mice exhibit several sites of hemorrhaging and red blood cells are detected throughout the myocardium red blood cells are detected throughout the myocardium

homeostasis/metabolism

cyanosis ( J:89696 )

• half of the mice that are born alive die within hours with signs of cyanosis

hypoxia ( J:89696 )

• mice delivered by Caesarian section develop transient signs of hypoxia (bluish skin)

growth/size/body

postnatal growth retardation ( J:89696 )

• mice exhibit the same growth rate as Rps6kb1^tm1Gtho homozygotes

reproductive system

decreased litter size ( J:89696 )

• mice produce small litters that exhibit a high incidence of perinatal lethality

Genotype
MGI:5829203

cx10

• Allelic Composition: Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho; Rps6kb2^tm1Gtho/Rps6kb2^tm1Gtho; Tg(Ins2-Akt1*)3Mbb/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:144599 )

• pancreatic beta cells are 4-fold larger than wild-type cells

neoplasm

neoplasm ( J:144599 )

N • mice do not develop insulinomas