Phenotypes associated with this allele

• Allele Symbol: Gsk3b^tm1Jrw
• Allele Name: targeted mutation 1, James R Woodgett
• Allele ID: MGI:1888887
• Summary: 9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gsk3b^tm1Jrw/Gsk3b^tm1Jrw	involves: 129 * C57BL/6J	MGI:2176838
hm2	Gsk3b^tm1Jrw/Gsk3b^tm1Jrw	involves: 129 * CD-1	MGI:3702521
ht3	Gsk3b^tm1Jrw/Gsk3b^+	involves: 129 * C57BL/6	MGI:3777977
ht4	Gsk3b^tm1Jrw/Gsk3b^+	involves: 129 * C57BL/6J	MGI:3578290
ht5	Gsk3b^tm1Grc/Gsk3b^tm1Jrw	involves: 129 * 129S6/SvEvTac * CD-1	MGI:3702520
cx6	Gsk3b^tm1Jrw/Gsk3b^+ Runx2^tm1Kish/Runx2^+	involves: 129 * 129P2/OlaHsd * C57BL/6	MGI:3778023
cx7	Gsk3b^tm1Jrw/Gsk3b^+ Tph2^tm1Mca/Tph2^tm1Mca	involves: 129 * 129S6/SvEvTac * C57BL/6J	MGI:3801154
cx8	Gsk3b^tm1Jrw/Gsk3b^+ Insr^tm1Dac/Insr^+	involves: 129 * C57BL/6J	MGI:3802542
cx9	Gsk3b^tm1Jrw/Gsk3b^+ Irs2^tm1Mfw/Irs2^tm1Mfw	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3802544

Genotype
MGI:2176838

hm1

• Allelic Composition: Gsk3b^tm1Jrw/Gsk3b^tm1Jrw
• Genetic Background: involves: 129 * C57BL/6J

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:63274 )

• between E13.5 and E14.5

• embryos could be rescued by i.p. injection of pregnant females at E10.5 or E11.5 with anti-TNF-alpha antibodies

liver/biliary system

abnormal liver morphology ( J:63274 )

• multifocal hemorrhagic degeneration

abnormal hepatocyte morphology ( J:63274 )

• apoptotic hepatocytes exhibiting pyknosis and karyorrhexis

Genotype
MGI:3702521

hm2

• Allelic Composition: Gsk3b^tm1Jrw/Gsk3b^tm1Jrw
• Genetic Background: involves: 129 * CD-1

mortality/aging

neonatal lethality, complete penetrance ( J:119186 )

• all die neonatally, unlike in previous studies where homozygotes died during mid-gestation

craniofacial

palatal shelves fail to meet at midline ( J:119186 )

• at E16.5, palatal shelves have rotated but do not meet at the midline

cleft secondary palate ( J:119186 )

• complete cleft of the secondary palate

skeleton

xiphoid process foramen ( J:119186 )

• often there are holes in the xiphoid cartilage

split sternum ( J:119186 )

• sternal bars are frequently bifurcated and the appearance of ossification centers is delayed

abnormal sternum ossification ( J:119186 )

• delay in ossification of the sternum is more obvious at early stages but by E18.5 levels of ossification in the sternum are sometimes similar to wild-type controls although the ossification centers are often in abnormal locations

delayed bone ossification ( J:119186 )

• delayed ossification of the skull, ear bones, and cranial base

• delay in ossification of the sternum is more obvious at early stages but by E18.5 levels of ossification in the sternum are sometimes similar to wild-type controls

digestive/alimentary system

palatal shelves fail to meet at midline ( J:119186 )

• at E16.5, palatal shelves have rotated but do not meet at the midline

cleft secondary palate ( J:119186 )

• complete cleft of the secondary palate

growth/size/body

palatal shelves fail to meet at midline ( J:119186 )

• at E16.5, palatal shelves have rotated but do not meet at the midline

cleft secondary palate ( J:119186 )

• complete cleft of the secondary palate

Genotype
MGI:3777977

ht3

• Allelic Composition: Gsk3b^tm1Jrw/Gsk3b⁺
• Genetic Background: involves: 129 * C57BL/6

Increased bone mass in Gsk3b^tm1Jrw/Gsk3b⁺ mice

skeleton

enhanced osteoblast differentiation ( J:129364 )

• ex vivo cultures of calvarial osteoblasts exhibit enhanced osteoblast differentiation

increased trabecular bone volume ( J:129364 )

increased compact bone thickness ( J:129364 )

increased bone mass ( J:129364 )

• increase in bone mass is seen in femurs

increased compact bone mass ( J:129364 )

• proximal tibiae show an increase in cortical bone mass, without abnormality in the growth plate

increased trabecular bone mass ( J:129364 )

• proximal tibiae show an increase in trabecular bone mass, without abnormality in the growth plate

abnormal skeleton physiology ( J:129364 )

abnormal osteoblast physiology ( J:129364 )

• ex vivo cultures of calvarial osteoblasts exhibit enhanced osteoblast differentiation and function as determined by alkaline phosphatase, Alizarin red, and von Kossa staining

increased bone ossification ( J:129364 )

• increase in trabecular bone volume and cortical thickness is accompanied by increases in parameters of bone formation

increased bone resorption ( J:129364 )

• bone resorption parameters are enhanced

cellular

enhanced osteoblast differentiation ( J:129364 )

• ex vivo cultures of calvarial osteoblasts exhibit enhanced osteoblast differentiation

abnormal osteoblast physiology ( J:129364 )

• ex vivo cultures of calvarial osteoblasts exhibit enhanced osteoblast differentiation and function as determined by alkaline phosphatase, Alizarin red, and von Kossa staining

Genotype
MGI:3578290

ht4

• Allelic Composition: Gsk3b^tm1Jrw/Gsk3b⁺
• Genetic Background: involves: 129 * C57BL/6J

behavior/neurological

decreased exploration in new environment ( J:97268 )

• reduced exploratory behavior using a "hole board" chamber test

• overall activity levels remained normal

behavioral despair ( J:97268 )

• reduced time spent immobile in a forced swim test

• overall activity levels remained normal

homeostasis/metabolism

abnormal glucose homeostasis ( J:135659 )

• improved insulin sensitivity

decreased circulating glucose level ( J:135659 )

• decreased fasting glucose level compared to the wild-type control

decreased circulating insulin level ( J:135659 )

• fasting and fed insulin levels were reduced

nervous system

decreased prepulse inhibition ( J:161844 )

• however, baseline startle response is normal

• at the 74 dB prepulse level

Genotype
MGI:3702520

ht5

• Allelic Composition: Gsk3b^tm1Grc/Gsk3b^tm1Jrw
• Genetic Background: involves: 129 * 129S6/SvEvTac * CD-1

mortality/aging

neonatal lethality, complete penetrance ( J:119186 )

• phenotype is identical to Gsk3b^tm1Jrw homozygotes

craniofacial

palatal shelves fail to meet at midline ( J:119186 )

• at E16.5, palatal shelves have rotated but do not meet at the midline

cleft secondary palate ( J:119186 )

• complete cleft of the secondary palate

skeleton

xiphoid process foramen ( J:119186 )

• often there are holes in the xiphoid cartilage

split sternum ( J:119186 )

• sternal bars are frequently bifurcated and the appearance of ossification centers is delayed

abnormal sternum ossification ( J:119186 )

• delay in ossification of the sternum is more obvious at early stages but by E18.5 levels of ossification in the sternum are sometimes similar to wild-type controls although the ossification centers are often in abnormal locations

delayed bone ossification ( J:119186 )

• delayed ossification of the skull, ear bones, and cranial base

• delay in ossification of the sternum is more obvious at early stages but by E18.5 levels of ossification in the sternum are sometimes similar to wild-type controls

digestive/alimentary system

palatal shelves fail to meet at midline ( J:119186 )

• at E16.5, palatal shelves have rotated but do not meet at the midline

cleft secondary palate ( J:119186 )

• complete cleft of the secondary palate

growth/size/body

palatal shelves fail to meet at midline ( J:119186 )

• at E16.5, palatal shelves have rotated but do not meet at the midline

cleft secondary palate ( J:119186 )

• complete cleft of the secondary palate

Genotype
MGI:3778023

cx6

• Allelic Composition: Gsk3b^tm1Jrw/Gsk3b⁺; Runx2^tm1Kish/Runx2⁺
• Genetic Background: involves: 129 * 129P2/OlaHsd * C57BL/6

Calvaria and clavicle abnormalities in Gsk3b^tm1Jrw/Gsk3b⁺, Runx2^tm1Kish/Runx2⁺, and Gsk3b^tm1Jrw/Gsk3b⁺ Runx2^tm1Kish/Runx2⁺ mice

skeleton

abnormal fontanelle morphology ( J:129364 )

• double heterozygotes exhibit a significant rescue of the fontanelle abnormalities that are seen in single Runx2 heterozygotes, although fontanelle closure is still slower than in wild-type

abnormal clavicle morphology ( J:129364 )

• double heterozygotes exhibit a significant rescue of clavicle abnormalities that are seen in single Runx2 heterozygotes, although the clavicles are still smaller and thinner than in wild-type

craniofacial

abnormal fontanelle morphology ( J:129364 )

• double heterozygotes exhibit a significant rescue of the fontanelle abnormalities that are seen in single Runx2 heterozygotes, although fontanelle closure is still slower than in wild-type

Genotype
MGI:3801154

cx7

• Allelic Composition: Gsk3b^tm1Jrw/Gsk3b⁺; Tph2^tm1Mca/Tph2^tm1Mca
• Genetic Background: involves: 129 * 129S6/SvEvTac * C57BL/6J

behavior/neurological

behavior/neurological phenotype ( J:131619 )

N • the Gsk3b allele rescues the aberrant behaviors observed in Tph2 homozygotes; mice exhibit normal immobility times in the tail suspension test, normal behavior in dark-light emergence test and normal aggression towards males

abnormal social investigation ( J:131619 )

• mutants display enhanced social investigation

Genotype
MGI:3802542

cx8

• Allelic Composition: Gsk3b^tm1Jrw/Gsk3b⁺; Insr^tm1Dac/Insr⁺
• Genetic Background: involves: 129 * C57BL/6J

homeostasis/metabolism

abnormal circulating glucose level ( J:135659 )

• decreased fasting glucose level relative to those in Insr^tm1Dac heterozygous mice

• the rate of glucose disposal and glucose infusion were increased relative to those in Insr^tm1Dac heterozygous mice

• hepatic glucose production is comparable to that in Insr^tm1Dac heterozygous mice

abnormal circulating insulin level ( J:135659 )

• the serum insulin values were significantly decreased relative to those in Insr^tm1Dac heterozygous mice in both the fasting and the fed state

• the values were significantly elevated relative to that in Gsk3b^tm1Jrw heterozygous mice

improved glucose tolerance ( J:135659 )

• compared to Insr^tm1Dac heterozygous mice

insulin resistance ( J:135659 )

• improved over Insr^tm1Dac heterozygous mice, but still insulin resistant compared to wild-type

endocrine/exocrine glands

decreased pancreatic beta cell mass ( J:135659 )

• reduced beta cell mass over Insr^tm1Dac heterozygous mice

Genotype
MGI:3802544

cx9

• Allelic Composition: Gsk3b^tm1Jrw/Gsk3b⁺; Irs2^tm1Mfw/Irs2^tm1Mfw
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

cellular

abnormal pancreatic islet cell apoptosis ( J:135659 )

• beta cell apoptosis was reduced to compared to that in Irs2^tm1Mfw homozygous mice, however still higher than wild-type control

increased pancreatic beta cell proliferation ( J:135659 )

• increased beta cell proliferation accounts for preservation of beta cell mass

• normal beta cell mass unlike Irs2^tm1Mfw homozygous mice

growth/size/body

growth/size/body region phenotype ( J:135659 )

N • retained normal weight through 12 weeks unlike Irs2^tm1Mfw homozygous mice

homeostasis/metabolism

abnormal circulating glucose level ( J:135659 )

• fed blood glucose concentration were significantly reduced relative to that in Irs2^tm1Mfw homozygous mice, though remained slightly higher than normal control

increased circulating glucose level ( J:135659 )

• fasting glucose levels were higher than in wild-type mice at both 6 weeks and 8 weeks of age

• fasting glucose level were reduced relative to that in Irs2^tm1Mfw homozygous mice at 8 weeks but not at 6 weeks

increased circulating insulin level ( J:135659 )

• both fasting and fed insulin levels were higher than in wild-type mice

insulin resistance ( J:135659 )

• insulin resistant compared to wild-type

• no improvement over Irs2^tm1Mfw homozygous mice

endocrine/exocrine glands

abnormal pancreatic islet cell apoptosis ( J:135659 )

• beta cell apoptosis was reduced to compared to that in Irs2^tm1Mfw homozygous mice, however still higher than wild-type control

increased pancreatic beta cell proliferation ( J:135659 )

• increased beta cell proliferation accounts for preservation of beta cell mass

• normal beta cell mass unlike Irs2^tm1Mfw homozygous mice