Phenotypes associated with this allele

• Allele Symbol: Gnas^tm3Lsw
• Allele Name: targeted mutation 3, Lee S Weinstein
• Allele ID: MGI:3043361
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Braf^tm1Cpri/Braf^tm1Cpri Gnas^tm3Lsw/Gnas^tm3Lsw Tg(TPO-cre)1Shk/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * FVB/NCr	MGI:5779648
cn2	Gnas^tm3Lsw/Gnas^tm3Lsw Ren1^tm2(cre)Gom/Ren1^+	involves: 129S6/SvEvTac * Black Swiss	MGI:3699334
cn3	Gnas^tm3Lsw/Gnas^tm3Lsw Tg(Col2a1-cre)1Rsjo/0	involves: 129S6/SvEvTac * FVB/N	MGI:3575290
cn4	Gnas^tm3Lsw/Gnas^tm3Lsw Tg(TPO-cre)1Shk/0	involves: 129S6/SvEvTac * FVB/NCr	MGI:5779650

Genotype
MGI:5779648

cn1

• Allelic Composition: Braf^tm1Cpri/Braf^tm1Cpri; Gnas^tm3Lsw/Gnas^tm3Lsw; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * FVB/NCr

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

endocrine/exocrine glands

increased thyroid tumor incidence ( J:168249 )

• mice develop smaller papillary thyroid tumors with greatly attenuated histological features resembling indolent papillary thyroid cancer in humans compared to single Braf^tm1Cpri conditional mutants

neoplasm

increased thyroid tumor incidence ( J:168249 )

• mice develop smaller papillary thyroid tumors with greatly attenuated histological features resembling indolent papillary thyroid cancer in humans compared to single Braf^tm1Cpri conditional mutants

Genotype
MGI:3699334

cn2

• Allelic Composition: Gnas^tm3Lsw/Gnas^tm3Lsw; Ren1^tm2(cre)Gom/Ren1⁺
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss

homeostasis/metabolism

decreased circulating aldosterone level ( J:118076 )

decreased circulating renin level ( J:118076 )

• exhibit reduced basal levels of renin expression and very low plasma renin concentrations

decreased urine osmolality ( J:118076 )

• urine osmolarity is only slightly above isotonicity and significantly lower than in controls

increased urine prostaglandin level ( J:118076 )

• excretion of PGE2 in urine is significantly higher

abnormal renin activity ( J:118076 )

• acute stimulation of renin release in response to furosemide, hydralazine, and isoproterenol are abolished

renal/urinary system

decreased urine osmolality ( J:118076 )

• urine osmolarity is only slightly above isotonicity and significantly lower than in controls

increased urine prostaglandin level ( J:118076 )

• excretion of PGE2 in urine is significantly higher

abnormal kidney physiology ( J:118076 )

• renin release by juxtaglomerular cells is significantly lower

decreased renal glomerular filtration rate ( J:118076 )

cardiovascular system

decreased mean systemic arterial blood pressure ( J:118076 )

• reduction in mean arterial blood pressure both at night and during the day

Genotype
MGI:3575290

cn3

• Allelic Composition: Gnas^tm3Lsw/Gnas^tm3Lsw; Tg(Col2a1-cre)1Rsjo/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

mortality/aging

neonatal lethality, complete penetrance ( J:97230 )

• all newborn pups died minutes after birth

craniofacial

domed cranium ( J:97230 )

homeostasis/metabolism

cyanosis ( J:97230 )

• all newborn pups had cyanosis

limbs/digits/tail

abnormal tibia morphology ( J:97230 )

• tibial epiphyses at P0.5 were decreased in length

• at P0.5, ectopic cartilage was present in the upper one-third portion of the frontal tibia and was clearly spatially separated from epiphyseal plate cartilage

short limbs ( J:97230 )

respiratory system

abnormal pulmonary alveolus morphology ( J:97230 )

• lung alveoli did not contain air and did not exhibit any obvious abnormalities in alveolar organization

skeleton

domed cranium ( J:97230 )

abnormal tibia morphology ( J:97230 )

• tibial epiphyses at P0.5 were decreased in length

• at P0.5, ectopic cartilage was present in the upper one-third portion of the frontal tibia and was clearly spatially separated from epiphyseal plate cartilage

abnormal long bone epiphyseal plate morphology ( J:97230 )

• the layer of periarticular chondrocytes was shortened, and the layer of proliferating chondrocytes was markedly shortened, whereas the size of the zone of hypertrophic chondrocytes was unaffected, and no differences in chondrocyte proliferation rate or cellular density within these zones was observed

• pool of proliferating chondrocytes was reduced, whereas the pool of postmitotic (hypertrophic) chondrocytes was maintained, indicating accelerated hypertrophic differentiation of growth plate chondrocytes

abnormal long bone epiphyseal plate proliferative zone ( J:97230 )

• the layer of proliferating chondrocytes was markedly shortened however no difference in the chondrocyte proliferation rate or cellular density was observed

abnormal long bone epiphysis morphology ( J:97230 )

• tibial epiphyses at P0.5 were decreased in length

abnormal cartilage development ( J:97230 )

• beginning at E18.5, mutants developed ectopic cartilage, comprised of prehypertrophic and hypertrophic chondrocytes, between the authentic cortical bone and the perichondrium in the tibia

• at P0.5, ectopic cartilage was present in the upper one-third portion of the frontal tibia and was clearly spatially separated from epiphyseal plate cartilage

Genotype
MGI:5779650

cn4

• Allelic Composition: Gnas^tm3Lsw/Gnas^tm3Lsw; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/NCr

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:168249 )

N • mice exhibit normal thyroid histology