Gsk3b<tm1Jrw> Targeted Allele Detail MGI Mouse (MGI:1888887)

Gsk3b^tm1Jrw
Targeted Allele Detail

Nomenclature

Symbol:	Gsk3b^tm1Jrw
Name:	glycogen synthase kinase 3 beta; targeted mutation 1, James R Woodgett
MGI ID:	MGI:1888887
Synonyms:	GSK-3beta^-, gsk3b-
Gene:	Gsk3b Location: Chr16:38089087-38246170 bp, + strand Genetic Position: Chr16, cytoband B4

Increased bone mass in Gsk3b^tm1Jrw/Gsk3b⁺ mice

Show the 2 image(s) involving this allele.

Mutation
origin

Germline Transmission:	Earliest citation of germline transmission: J:63274
Parent Cell Line:	Not Specified (ES Cell)
Strain of Origin:	129

Mutation
description

Allele Type:	Targeted (knock-out)
Mutations:	Insertion, Intragenic deletion
	A neomycin resistance cassette replaced an exon encoding the ATP-binding loop. Southern and Western blots of embryonic fibroblasts (E12.5) showed no detectable DNA and protein of the targeted gene, respectively. (J:63274)

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:	Mouse Strains: 0 strains available Cell Lines: 0 lines available
Carrying any Gsk3b Mutation:	82 strains or lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	hm1	hm2	ht3	ht4	ht5	cx6	cx7	cx8	cx9
behavior/neurological					√			√
behavior/neurological phenotype								N
behavioral despair					√
decreased exploration in new environment					√
abnormal social investigation								√
		hm1	hm2	ht3	ht4	ht5	cx6	cx7	cx8	cx9
craniofacial			√			√	√
cleft palate			√			√
abnormal fontanelle morphology							√
		hm1	hm2	ht3	ht4	ht5	cx6	cx7	cx8	cx9
digestive/alimentary system			√			√			√	√
cleft palate			√			√
abnormal pancreatic beta cell morphology										√
decreased pancreatic beta cell mass									√
		hm1	hm2	ht3	ht4	ht5	cx6	cx7	cx8	cx9
endocrine/exocrine glands									√	√
abnormal pancreatic beta cell morphology										√
decreased pancreatic beta cell mass									√
		hm1	hm2	ht3	ht4	ht5	cx6	cx7	cx8	cx9
growth/size										N
growth/size phenotype										N
		hm1	hm2	ht3	ht4	ht5	cx6	cx7	cx8	cx9
homeostasis/metabolism					√				√	√
abnormal glucose homeostasis					√
abnormal circulating glucose level									√	√
decreased circulating glucose level					√
increased circulating glucose level										√
abnormal circulating insulin level									√
decreased circulating insulin level					√
increased circulating insulin level										√
improved glucose tolerance									√
insulin resistance									√	√
		hm1	hm2	ht3	ht4	ht5	cx6	cx7	cx8	cx9
lethality/prenatal-perinatal		√	√			√
lethality throughout fetal growth and development		√
neonatal lethality			√			√
		hm1	hm2	ht3	ht4	ht5	cx6	cx7	cx8	cx9
liver/biliary system		√
abnormal liver morphology		√
abnormal hepatocyte morphology		√
		hm1	hm2	ht3	ht4	ht5	cx6	cx7	cx8	cx9
skeleton			√	√		√	√
xiphoid process foramen			√			√
split sternum			√			√
abnormal cancellous bone morphology				√
abnormal cortical bone morphology				√
increased bone mass				√
abnormal osteogenesis				√
abnormal sternum ossification			√			√
delayed bone ossification			√			√
abnormal skeleton physiology				√
increased bone resorption				√
abnormal osteoblast physiology				√
abnormal fontanelle morphology							√
abnormal clavicle morphology							√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
hm1	Gsk3b^tm1Jrw/Gsk3b^tm1Jrw	involves: 129 * C57BL/6J
lethality/prenatal-perinatal lethality throughout fetal growth and development (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	Allelic Composition	Genetic Background
hm2	Gsk3b^tm1Jrw/Gsk3b^tm1Jrw	involves: 129 * CD-1
lethality/prenatal-perinatal neonatal lethality (J:119186) all die neonatally, unlike in previous studies where homozygotes died during mid-gestation craniofacial cleft palate (J:119186) complete cleft of the secondary palate skeleton 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 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 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 cleft palate (J:119186) complete cleft of the secondary palate
Genotype	Allelic Composition	Genetic Background
ht3	Gsk3b^tm1Jrw/Gsk3b⁺	involves: 129 * C57BL/6
Increased bone mass in Gsk3b^tm1Jrw/Gsk3b⁺ mice skeleton abnormal cancellous bone morphology (J:129364) proximal tibiae show an increase in trabecular bones, without abnormality in the growth plate abnormal cortical bone morphology (J:129364) proximal tibiae show an increase in cortical bones, without abnormality in the growth plate increased bone mass (J:129364) increase in bone mass is seen in femurs abnormal osteogenesis (J:129364) increase in trabecular bone volume and cortical thickness is accompanied by increases in parameters of bone formation abnormal skeleton physiology (J:129364) increased bone resorption (J:129364) bone resorption parameters are enhanced 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	Allelic Composition	Genetic Background
ht4	Gsk3b^tm1Jrw/Gsk3b⁺	involves: 129 * C57BL/6J
behavior/neurological behavioral despair (J:97268) reduced time spent immobile in a forced swim test overall activity levels remained normal decreased exploration in new environment (J:97268) reduced exploratory behavior using a "hole board" chamber 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
Genotype	Allelic Composition	Genetic Background
ht5	Gsk3b^tm1Grc/Gsk3b^tm1Jrw	involves: 129 * 129S6/SvEvTac * CD-1
lethality/prenatal-perinatal neonatal lethality (J:119186) phenotype is identical to Gsk3b^tm1Jrw homozygotes craniofacial cleft palate (J:119186) complete cleft of the secondary palate skeleton 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 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 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 cleft palate (J:119186) complete cleft of the secondary palate
Genotype	Allelic Composition	Genetic Background
cx6	Gsk3b^tm1Jrw/Gsk3b⁺ Runx2^tm1Kish/Runx2⁺	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	Allelic Composition	Genetic Background
cx7	Gsk3b^tm1Jrw/Gsk3b⁺ Tph2^tm1Mca/Tph2^tm1Mca	involves: 129 * 129S6/SvEvTac * C57BL/6J
behavior/neurological behavior/neurological phenotype (J:131619) 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	Allelic Composition	Genetic Background
cx8	Gsk3b^tm1Jrw/Gsk3b⁺ Insr^tm1Dac/Insr⁺	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 digestive/alimentary system decreased pancreatic beta cell mass (J:135659) reduced beta cell mass over Insr^tm1Dac heterozygous mice endocrine/exocrine glands decreased pancreatic beta cell mass (J:135659) reduced beta cell mass over Insr^tm1Dac heterozygous mice
Genotype	Allelic Composition	Genetic Background
cx9	Gsk3b^tm1Jrw/Gsk3b⁺ Irs2^tm1Mfw/Irs2^tm1Mfw	involves: 129 * C57BL/6J
growth/size growth/size phenotype (J:135659) 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 digestive/alimentary system abnormal pancreatic beta cell morphology (J:135659) increased beta cell proliferation accounts for preservation of beta cell mass beta cell apoptosis was reduced to compared to that in Irs2^tm1Mfw homozygous mice, however still higher than wild-type control normal beta cell mass unlike Irs2^tm1Mfw homozygous mice endocrine/exocrine glands abnormal pancreatic beta cell morphology (J:135659) increased beta cell proliferation accounts for preservation of beta cell mass beta cell apoptosis was reduced to compared to that in Irs2^tm1Mfw homozygous mice, however still higher than wild-type control normal beta cell mass unlike Irs2^tm1Mfw homozygous mice

References

Original:	J:63274 Hoeflich KP et al., "Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation [see comments]" Nature 2000 Jul 6;406(6791):86-90
All:	16 reference(s)

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