Phenotypes associated with this allele

• Allele Symbol: Gnaq^tm2Soff
• Allele Name: targeted mutation 2, Stefan Offermanns
• Allele ID: MGI:2446355
• Summary: 11 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Cd19^tm1(cre)Cgn/Cd19^+ Gna11^tm1Soff/Gna11^tm1Soff Gnaq^tm2Soff/Gnaq^tm2Soff	B6N.129-Cd19^tm1(cre)Cgn Gna11^tm1Soff Gnaq^tm2Soff	MGI:3699321
cn2	Gna11^tm1Soff/Gna11^tm1Soff Gnaq^tm2Soff/Gnaq^tm2Soff Tg(Tek-icre/ERT2)1Soff/0	B6N.Cg-Gna11^tm1Soff Gnaq^tm2Soff Tg(Tek-icre/ERT2)1Soff	MGI:5800455
cn3	Gna11^tm1Soff/Gna11^tm1Soff Gnaq^tm2Soff/Gnaq^tm2Soff Myl2^tm1(cre)Krc/Myl2^+	involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd * C57BL	MGI:3706996
cn4	Gna11^tm1Soff/Gna11^tm1Soff Gnaq^tm2Soff/Gnaq^tm2Soff Tg(PTH-cre)4167Slib/0	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6	MGI:3796551
cn5	Gna11^tm1Soff/Gna11^+ Gnaq^tm2Soff/Gnaq^tm2Soff Tg(PTH-cre)4167Slib/0	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6	MGI:3796552
cn6	Gna11^tm1Soff/Gna11^tm1Soff Gnaq^tm2Soff/Gnaq^+ Tg(PTH-cre)4167Slib/0	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6	MGI:3796553
cn7	Gna11^tm1Soff/Gna11^tm1Soff Gnaq^tm2Soff/Gnaq^tm2Soff Tg(Mpz-cre)94Imeg/0	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6	MGI:3796532
cn8	Gna11^tm1Soff/Gna11^tm1Soff Gnaq^tm2Soff/Gnaq^tm2Soff Tg(Tg-cre)1Soff/0	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6	MGI:3796562
cn9	Gna11^tm1Soff/Gna11^tm1Soff Gnaq^tm2Soff/Gnaq^tm2Soff Tg(Camk2a-cre)1Gsc/0	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * FVB/N	MGI:3796547
cn10	Gna11^tm1Soff/Gna11^tm1Soff Gnaq^tm2Soff/Gnaq^tm2Soff X/Tg(Myh11-icre/ERT2)1Soff	involves: 129P2/OlaHsd * 129S7/SvEvBrd * FVB/N	MGI:3819271
cn11	Gna11^tm1Soff/Gna11^tm1Soff Gnaq^tm2Soff/Gnaq^tm2Soff Tg(Tek-icre/ERT2)1Soff/?	involves: 129P2/OlaHsd * 129S7/SvEvBrd * FVB/N	MGI:3837458

Genotype
MGI:3699321

cn1

• Allelic Composition: Cd19^tm1(cre)Cgn/Cd19⁺; Gna11^tm1Soff/Gna11^tm1Soff; Gnaq^tm2Soff/Gnaq^tm2Soff
• Genetic Background: B6N.129-Cd19^tm1(cre)Cgn Gna11^tm1Soff Gnaq^tm2Soff

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

hematopoietic system

hematopoietic system phenotype ( J:117663 )

N • double deficient B cells do not show abnormalities is lysophospholipid-induced adhesion

Genotype
MGI:5800455

cn2

• Allelic Composition: Gna11^tm1Soff/Gna11^tm1Soff; Gnaq^tm2Soff/Gnaq^tm2Soff; Tg(Tek-icre/ERT2)1Soff/0
• Genetic Background: B6N.Cg-Gna11^tm1Soff Gnaq^tm2Soff Tg(Tek-icre/ERT2)1Soff

cardiovascular system

increased susceptibility to hypertension ( J:224523 )

• in response to tamoxifen

decreased vasodilation ( J:224523 )

• almost complete lost of dilation in response to flow

• inhibited acethylcholine-induced vasodilation

• however, vasodilation in response to sodium nitroprusside and vasoconstriction in response to phenylephrine are normal

abnormal vascular wound healing ( J:224523 )

• in response to ligation of the external carotid artery, mice exhibit a strong reduction in neointima formation compared with control mice

• however, there is no change in the diameter of the common carotid artery

homeostasis/metabolism

abnormal vascular wound healing ( J:224523 )

• in response to ligation of the external carotid artery, mice exhibit a strong reduction in neointima formation compared with control mice

• however, there is no change in the diameter of the common carotid artery

decreased nitrate level ( J:224523 )

• decreased in the plasma of tamoxifen-treated mice

muscle

decreased vasodilation ( J:224523 )

• almost complete lost of dilation in response to flow

• inhibited acethylcholine-induced vasodilation

• however, vasodilation in response to sodium nitroprusside and vasoconstriction in response to phenylephrine are normal

Genotype
MGI:3706996

cn3

• Allelic Composition: Gna11^tm1Soff/Gna11^tm1Soff; Gnaq^tm2Soff/Gnaq^tm2Soff; Myl2^tm1(cre)Krc/Myl2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd * C57BL

mortality/aging

perinatal lethality, incomplete penetrance ( J:77461 )

• about 75% die perinatally

cardiovascular system

heart hypoplasia ( J:77461 )

• pups that die perinatally exhibit varying degrees of myocardial hypoplasia

• however, mutants that survive to adulthood, appear normal and are fertile

decreased response of heart to induced stress ( J:77461 )

• homozygotes surviving to adulthood exhibit no ventricular hypertrophy in response to pressure-overload induced by aortic constriction, indicating a complete lack of a hypertrophic response

homeostasis/metabolism

decreased response of heart to induced stress ( J:77461 )

• homozygotes surviving to adulthood exhibit no ventricular hypertrophy in response to pressure-overload induced by aortic constriction, indicating a complete lack of a hypertrophic response

Genotype
MGI:3796551

cn4

• Allelic Composition: Gna11^tm1Soff/Gna11^tm1Soff; Gnaq^tm2Soff/Gnaq^tm2Soff; Tg(PTH-cre)4167Slib/0
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6

mortality/aging

postnatal lethality ( J:116986 )

growth/size/body

short snout ( J:116986 )

• anterior-posterior shortening of craniofacial complex is most pronounced in the snout

decreased body weight ( J:116986 )

• drastically reduced P9 compared to controls

decreased body length ( J:116986 )

• drastically reduced P9 compared to controls

proportional dwarf ( J:116986 )

• severe dwarfism by P9

postnatal growth retardation ( J:116986 )

• internal organs are reduced in size according to general growth retardation of mutants

craniofacial

wide cranial sutures ( J:116986 )

• sutures are much wider than in controls

domed cranium ( J:116986 )

• doming of cranial vault is observed at P9

short snout ( J:116986 )

• anterior-posterior shortening of craniofacial complex is most pronounced in the snout

skeleton

wide cranial sutures ( J:116986 )

• sutures are much wider than in controls

domed cranium ( J:116986 )

• doming of cranial vault is observed at P9

rachitic rosary ( J:116986 )

• bulging of costochondral junction (rachitic rosary) is observed in ribs

decreased bone mineral density ( J:116986 )

• severe osteopenia is observed throughout the skeleton

abnormal epiphyseal plate morphology ( J:116986 )

• all growth plates display rachitic changes

abnormal bone mineralization ( J:116986 )

• barely detectable in bones of paws and caudal vertebrae at P9

• mineralization of ventral ribs is lacking

delayed endochondral bone ossification ( J:116986 )

• noted in cervical and caudal vertebrae, bones of paws, and all long bones

• epiphyseal ossification of femur and tibia is lacking at P9

increased bone resorption ( J:116986 )

• evidence of bone resorption is observed in mutants at P9

endocrine/exocrine glands

abnormal parathyroid gland morphology ( J:116986 )

• proliferation of cells is significantly enhance compared to controls

small thyroid gland ( J:116986 )

• massively growth-retarded

homeostasis/metabolism

increased circulating parathyroid hormone level ( J:116986 )

• significantly increased levels are observed at P9

increased urine calcium level ( J:116986 )

• urine calcium level is strongly increased

renal/urinary system

increased urine calcium level ( J:116986 )

• urine calcium level is strongly increased

respiratory system

abnormal larynx morphology ( J:116986 )

• massively growth-retarded

Genotype
MGI:3796552

cn5

• Allelic Composition: Gna11^tm1Soff/Gna11⁺; Gnaq^tm2Soff/Gnaq^tm2Soff; Tg(PTH-cre)4167Slib/0
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6

growth/size/body

decreased body weight ( J:116986 )

• reduced at P9 compared to controls

homeostasis/metabolism

increased circulating parathyroid hormone level ( J:116986 )

• levels are increased compared to controls at P9

abnormal circulating calcium level ( J:116986 )

• increased relative to controls

abnormal urine calcium level ( J:116986 )

• increased relative to controls at P9

renal/urinary system

abnormal urine calcium level ( J:116986 )

• increased relative to controls at P9

Genotype
MGI:3796553

cn6

• Allelic Composition: Gna11^tm1Soff/Gna11^tm1Soff; Gnaq^tm2Soff/Gnaq⁺; Tg(PTH-cre)4167Slib/0
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6

growth/size/body

decreased body weight ( J:116986 )

• reduced at P9 compared to controls

homeostasis/metabolism

increased circulating parathyroid hormone level ( J:116986 )

• levels are increased compared to controls

abnormal circulating calcium level ( J:116986 )

• increased relative to controls at P9

abnormal urine calcium level ( J:116986 )

• increased relative to controls

renal/urinary system

abnormal urine calcium level ( J:116986 )

• increased relative to controls

Genotype
MGI:3796532

cn7

• Allelic Composition: Gna11^tm1Soff/Gna11^tm1Soff; Gnaq^tm2Soff/Gnaq^tm2Soff; Tg(Mpz-cre)94Imeg/0
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6

craniofacial

craniofacial phenotype ( J:131382 )

N • incisive alveolar bone in distal mandibular region is relatively well-developed

abnormal sphenoid bone morphology ( J:131382 )

abnormal alisphenoid bone morphology ( J:131382 )

• lamina obturans is duplicated

abnormal pterygoid process morphology ( J:131382 )

• duplicated in mutants

abnormal hyoid bone morphology ( J:131382 )

• hyoid is not fused to basisphenoid in all cases; body of hyoid has extended ossification center and is fused to lesser hyoid horn and often with superior horn of thyroid similar to Ednrb-knock-in homozygotes

lower jaw to upper jaw transformation ( J:131382 )

• maxillary bones are duplicated in mandibular region

abnormal palatine bone morphology ( J:131382 )

• duplication of palatine bone is observed

abnormal zygomatic bone morphology ( J:131382 )

• duplication of jugal bone in mandibular region is observed

skeleton

abnormal sphenoid bone morphology ( J:131382 )

abnormal alisphenoid bone morphology ( J:131382 )

• lamina obturans is duplicated

abnormal pterygoid process morphology ( J:131382 )

• duplicated in mutants

abnormal hyoid bone morphology ( J:131382 )

• hyoid is not fused to basisphenoid in all cases; body of hyoid has extended ossification center and is fused to lesser hyoid horn and often with superior horn of thyroid similar to Ednrb-knock-in homozygotes

lower jaw to upper jaw transformation ( J:131382 )

• maxillary bones are duplicated in mandibular region

abnormal palatine bone morphology ( J:131382 )

• duplication of palatine bone is observed

abnormal zygomatic bone morphology ( J:131382 )

• duplication of jugal bone in mandibular region is observed

Genotype
MGI:3796562

cn8

• Allelic Composition: Gna11^tm1Soff/Gna11^tm1Soff; Gnaq^tm2Soff/Gnaq^tm2Soff; Tg(Tg-cre)1Soff/0
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:127484 )

N • as mutants age, no significant differences in thyroid size or weight is observed relative to wild-type

abnormal thyroid gland morphology ( J:127484 )

• at 6 months of age, histology is altered; follicular structure is disturbed with few normal follicles remaining

• no increase in thyroid gland weight is observed in 6-8 week-old mice treated with TSH (thyroid stimulating hormone) for 1 week, whereas wild-type mice show a 100% increase in thyroid weight; glands in mutants actually decrease in weight due to slight decrease in follicular lumen size

• no increase in thyrocyte number is observed after TSH treatment in contrast to increase seen in wild-type; thryocytes show hypertrophic response to TSH treatment

• after TSH treatment, colloid area is reduced unlike wild-type thyroids

• mutant thyroids show no response to goitrogenic diet, whereas wild-type mice readily develop hyperplastic goiters

abnormal thyroid follicular cell morphology ( J:127484 )

• cells are often enlarged, columnar and have large nuclei at 6 months of age

abnormal thyroid gland physiology ( J:127484 )

• TSH-induced thyroid hormone release is almost entirely abrogated in mutants

• impaired pinocytic uptake of colloid and reduction in pinocytic vesicle formation in thyroid follicular epithelium upon TSH stimulation is observed in mutants versus wild-type

decreased activity of thyroid gland ( J:127484 )

• after 6 months of age, about half of animals display overt hypothyroidism

homeostasis/metabolism

decreased circulating thyroxine level ( J:127484 )

• at 6 months, mice show low T4 levels compared to wild-type

increased circulating thyroid-stimulating hormone level ( J:127484 )

• beginning at 2 months of age, TSH (thyroid stimulating hormone) plasma levels start to rise and are significantly higher than wild-type at 6 months of age

Genotype
MGI:3796547

cn9

• Allelic Composition: Gna11^tm1Soff/Gna11^tm1Soff; Gnaq^tm2Soff/Gnaq^tm2Soff; Tg(Camk2a-cre)1Gsc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * FVB/N

mortality/aging

premature death ( J:111559 )

• age-dependent reduction in survival due to tonic-clonic seizures

nervous system

seizures ( J:111559 )

• around 3 months of age, mice show spontaneous epileptic seizures; animals affected and seizure number per animal increase with age

• mutants show reduced latency to seizure onset and tendency to have stronger seizures when treated with kainic acid or PTZ than wild-type; seizure-induced lethality is greatly increased

• blockade of cannabinoid receptors does not result in aggravation of kainic acid-induced seizures in mutants but does in wild-type controls

• treatment of mutants with endocannabinoid reuptake inhibitor causes a significant amelioration of kainic acid induced seizures

clonic seizures ( J:111559 )

• most seizures are myoclonic

tonic-clonic seizures ( J:111559 )

• some animals exhibit tonic-clonic seizures with age

hippocampal neuron degeneration ( J:111559 )

• older animals particularly those with symptomatic epilepsy show neuronal degeneration in CA1 region

gliosis ( J:111559 )

• older mice display reactive gliosis in CA1 region of hippocampus

abnormal nervous system electrophysiology ( J:123222 )

• no CCK4-induced (cholecystokinin receptor₂ agonist) current is detected in amygdala slices while inward current response in wild-type is unaffected

behavior/neurological

seizures ( J:111559 )

• around 3 months of age, mice show spontaneous epileptic seizures; animals affected and seizure number per animal increase with age

• mutants show reduced latency to seizure onset and tendency to have stronger seizures when treated with kainic acid or PTZ than wild-type; seizure-induced lethality is greatly increased

• blockade of cannabinoid receptors does not result in aggravation of kainic acid-induced seizures in mutants but does in wild-type controls

• treatment of mutants with endocannabinoid reuptake inhibitor causes a significant amelioration of kainic acid induced seizures

clonic seizures ( J:111559 )

• most seizures are myoclonic

tonic-clonic seizures ( J:111559 )

• some animals exhibit tonic-clonic seizures with age

Genotype
MGI:3819271

cn10

• Allelic Composition: Gna11^tm1Soff/Gna11^tm1Soff; Gnaq^tm2Soff/Gnaq^tm2Soff; X/Tg(Myh11-icre/ERT2)1Soff
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * FVB/N

cardiovascular system

decreased systemic arterial blood pressure ( J:141641 )

♂ • tamoxifen-treated mice exhibit decreased blood pressure following treatment with angiotensin II, vasopressin and endothelin compared to in wild-type mice

♂ • tamoxifen-treated mice exposed to DOCA-salt do not develop hypertension and DOCA-salt treated mice exposed to tamoxifen following the onset of hypertension exhibit a drop in blood pressure compared to in similarly treated wild-type mice

decreased mean systemic arterial blood pressure ( J:141641 )

♂ • following a normal transient increase in mean arterial blood pressure upon treatment with tamoxifen, mice exhibit a drop in mean arterial blood pressure below normal levels

♂ • slight in the absence of tamoxifen induction

decreased vasoconstriction ( J:141641 )

♂ • tamoxifen-treated mice fail to exhibit vasocontractile effects induced by phenylephrine or angiotensin II as do wild-type mice

♂ • tamoxifen-treated mice exhibit reduced vasocontraction in response to serotonine, vasopressin, U46619 and endothelin-1 compared to similarly treated wild-type mice

muscle

decreased vasoconstriction ( J:141641 )

♂ • tamoxifen-treated mice fail to exhibit vasocontractile effects induced by phenylephrine or angiotensin II as do wild-type mice

♂ • tamoxifen-treated mice exhibit reduced vasocontraction in response to serotonine, vasopressin, U46619 and endothelin-1 compared to similarly treated wild-type mice

Genotype
MGI:3837458

cn11

• Allelic Composition: Gna11^tm1Soff/Gna11^tm1Soff; Gnaq^tm2Soff/Gnaq^tm2Soff; Tg(Tek-icre/ERT2)1Soff/?
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * FVB/N

cardiovascular system

decreased vascular permeability ( J:146132 )

• in mice with induction of cre recombinase, basal permeability is lower than controls

• vascular permeability does not increase above basal levels in response to histamine, IgE, platelet-activating factor (PAF), lysophosphatidic acid (LPA), or F2r-activating peptide

• mice are resistant to death resulting from PAF-induced shock

immune system

immune system phenotype ( J:146132 )

N • while resistant to shock induced by IgE or vasoactive substances, mice are not resistant to shock induced by LPS

decreased susceptibility to type I hypersensitivity reaction ( J:146132 )

• tamoxifen treated mice are resistant to IgE-induced anaphylactic shock

• in an anti-DNP model, mice only have transient drops in systolic blood pressure compared to the sustained (>90 min) drops that occur in controls

• in an anti-BSA model, all mice survive anaphylactic challenge with only moderate decreases in body temperature compared to controls that suffer from severe hypothermia and death within 20 min of challenge