Phenotypes associated with this allele

• Allele Symbol: Gnas^tm5.1Lsw
• Allele Name: targeted mutation 5.1, Lee S Weinstein
• Allele ID: MGI:3609165
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Gnas^tm5.1Lsw/Gnas^tm5.1Lsw Gt(ROSA)26Sor^tm1(CAG-Mapt/GFP)Uboe/Gt(ROSA)26Sor^+ Or8a1^tm28(cre)Mom/Or8a1^tm27Mom	involves: 129P2/OlaHsd * 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6J	MGI:5788923
cn2	Gnas^tm5.1Lsw/Gnas^tm5.1Lsw Tg(Gfy-cre)1Yyos/?	involves: 129S6/SvEvTac * Black Swiss * C57BL/6J * FVB/N	MGI:5788551
cn3	Gnas^tm5.1Lsw/Gnas^tm5.1Lsw Tg(Alb1-cre)1Dlr/?	involves: 129S6/SvEvTac * Black Swiss * FVB/N	MGI:3610384
cn4	Gnas^tm5.1Lsw/Gnas^tm5.1Lsw H2az2^Tg(Wnt1-cre)11Rth/H2az2^+	involves: 129S6/SvEvTac * C57BL/6J * CBA/J	MGI:7367344
cn5	Gnas^tm5.1Lsw/Gnas^tm5.1Lsw Tg(Nes-cre)1Atp/0	involves: 129S6/SvEvTac * FVB/N	MGI:7367354
cn6	Gnas^tm5.1Lsw/Gnas^tm5.1Lsw Tg(Slc5a2-cre)1Tauc/0	involves: C57BL/6 * DBA/2	MGI:5818291
cn7	Gnas^tm5.1Lsw/Gnas^tm5.1Lsw Tg(Fabp4-cre)1Abel/0	involves: FVB	MGI:6102945

Genotype
MGI:5788923

cn1

• Allelic Composition: Gnas^tm5.1Lsw/Gnas^tm5.1Lsw; Gt(ROSA)26Sor^{tm1(CAG-Mapt/GFP)Uboe}/Gt(ROSA)26Sor⁺; Or8a1^tm28(cre)Mom/Or8a1^tm27Mom
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6J

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

taste/olfaction

taste/olfaction phenotype ( J:233447 )

N • axons of OLFR151 expressing olfactory sensory neurons appear to co-converge and coalesce in glomerular formation correctly despite G-protein disruption during development

Genotype
MGI:5788551

cn2

• Allelic Composition: Gnas^tm5.1Lsw/Gnas^tm5.1Lsw; Tg(Gfy-cre)1Yyos/?
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss * C57BL/6J * FVB/N

taste/olfaction

taste/olfaction phenotype ( J:233447 )

N • formation of olfactory bulb glomeruli appears normal despite G-protein disruption in basal stem cells and some immature olfactory sensory neurons

Genotype
MGI:3610384

cn3

• Allelic Composition: Gnas^tm5.1Lsw/Gnas^tm5.1Lsw; Tg(Alb1-cre)1Dlr/?
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss * FVB/N

liver/biliary system

increased liver weight ( J:102504 )

• approximately 25% greater than control

increased liver glycogen level ( J:102504 )

• in the fed state

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:102504 )

N • food intake measured over 14 days was normal

hypoglycemia ( J:102504 )

• in fed mutant mice

increased circulating glucagon level ( J:102504 )

• very high glucagon and glucagon-like peptide-1

decreased circulating insulin level ( J:102504 )

• in fed mutant mice

increased circulating triglyceride level ( J:102504 )

• in fasted mutant mice

abnormal energy expenditure ( J:102504 )

• mutant mice had resting and total energy expenditure rate at 30 degree

• resting or total energy expenditure rate or activity level at ambient temperature are normal

improved glucose tolerance ( J:102504 )

• increased glucose-stimulated insulin secretion

• increased insulin sensitivity in liver and muscle

increased liver glycogen level ( J:102504 )

• in the fed state

adipose tissue

decreased total body fat amount ( J:102504 )

• reduced adiposity

endocrine/exocrine glands

pancreatic islet hyperplasia ( J:102504 )

• alpha cell hyperplasia with les uniform cellular size and appearance

increased pancreas weight ( J:102504 )

• mutant mice had increased pancreas weights

growth/size/body

increased pancreas weight ( J:102504 )

• mutant mice had increased pancreas weights

increased liver weight ( J:102504 )

• approximately 25% greater than control

Genotype
MGI:7367344

cn4

• Allelic Composition: Gnas^tm5.1Lsw/Gnas^tm5.1Lsw; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * CBA/J

mortality/aging

neonatal lethality, complete penetrance ( J:254756 )

• mice are born at expected Mendelian ratios; however, all neonates die within hours after birth

homeostasis/metabolism

cyanosis ( J:254756 )

• newborns become progressively cyanotic

respiratory system

absent nasal capsule ( J:254756 )

• at P0, the nasal capsule is missing

abnormal nasal septum cartilage morphology ( J:254756 )

• at E17.5, the nasal septum cartilage is abnormally ossified and malformed

abnormal thyroid cartilage morphology ( J:254756 )

• thyroid cartilage is abnormally ossified at P0

respiratory distress ( J:254756 )

behavior/neurological

abnormal suckling behavior ( J:254756 )

• newborns are unable to suckle

craniofacial

abnormal craniofacial morphology ( J:254756 )

• at P0, all mice exhibit severe craniofacial malformations

• however, embryos are grossly normal at E10.5 and E12.5

abnormal craniofacial bone morphology ( J:254756 )

• newborns show severe craniofacial skeleton defects due to accelerated osteochondrogenic differentiation; the NCC-derived nasal capsule, maxilla, premaxilla, mandible, tympanic ring and body of hyoid bone are absent or severely malformed

• in contrast, mesoderm-derived skeleton elements including the parietal, lateral portion of the interparietal, supraoccipital, exoccipital, basioccipital and otic capsule are formed normally

abnormal hyoid bone morphology ( J:254756 )

• hyoid bone is heavily ossified at P0

abnormal hyoid bone body morphology ( J:254756 )

• newborns exhibit an over-ossified body of the hyoid bone

• premature ossification in the body of hyoid bone is first seen at E15.5

abnormal incisor morphology ( J:254756 )

• incisor tip is abnormally ossified at E14.5 and E15.5

abnormal mandible morphology ( J:254756 )

• newborns exhibit a hypoplastic and malformed mandible

• mandibular bone is heavily ossified at P0

absent mandibular angle ( J:254756 )

• at P0, the angular process is missing

absent mandibular condyloid process ( J:254756 )

• at P0, the condylar process is missing

absent mandibular coronoid process ( J:254756 )

• at P0, the coronoid process is missing

mandible hypoplasia ( J:254756 )

short mandible ( J:254756 )

• at E16.5, E18.5 and P0, the mandible is severely shortened

abnormal maxilla morphology ( J:254756 )

• newborns exhibit a hypoplastic and malformed maxilla

abnormal premaxilla morphology ( J:254756 )

• newborns exhibit a hypoplastic and malformed premaxilla

maxilla hypoplasia ( J:254756 )

short maxilla ( J:254756 )

• at E16.5, E18.5 and P0, the maxilla is severely shortened

domed cranium ( J:254756 )

• at P0, mice exhibit a domed skull

palate bone hypoplasia ( J:254756 )

• neonatal palatal bones are severely hypoplastic and thus palate is cleft

absent nasal capsule ( J:254756 )

• at P0, the nasal capsule is missing

palatal shelves fail to meet at midline ( J:254756 )

• palatal shelves are well developed and elevate to the horizontal position above tongue but fail to elongate or fuse at E14.5

• however, in vitro, palatal shelves show complete fusion with normal disappearance of the medial edge epithelium after 72 hours in organ culture

round face ( J:254756 )

• at E14.5, embryos exhibit a round face

complete cleft palate ( J:254756 )

• newborns exhibit a complete cleft palate caused by craniofacial skeleton defects

abnormal tongue morphology ( J:254756 )

• at E16.5 and E18.5, the tongue is arched rather than flat

protruding tongue ( J:254756 )

• at E16.5, E18.5 and P0, mice exhibit an exposed (protuberant) tongue

abnormal nasal septum cartilage morphology ( J:254756 )

• at E17.5, the nasal septum cartilage is abnormally ossified and malformed

short snout ( J:254756 )

• at E14.5, embryos exhibit a short snout

skeleton

abnormal craniofacial bone morphology ( J:254756 )

• newborns show severe craniofacial skeleton defects due to accelerated osteochondrogenic differentiation; the NCC-derived nasal capsule, maxilla, premaxilla, mandible, tympanic ring and body of hyoid bone are absent or severely malformed

• in contrast, mesoderm-derived skeleton elements including the parietal, lateral portion of the interparietal, supraoccipital, exoccipital, basioccipital and otic capsule are formed normally

abnormal hyoid bone morphology ( J:254756 )

• hyoid bone is heavily ossified at P0

abnormal hyoid bone body morphology ( J:254756 )

• newborns exhibit an over-ossified body of the hyoid bone

• premature ossification in the body of hyoid bone is first seen at E15.5

abnormal incisor morphology ( J:254756 )

• incisor tip is abnormally ossified at E14.5 and E15.5

abnormal mandible morphology ( J:254756 )

• newborns exhibit a hypoplastic and malformed mandible

• mandibular bone is heavily ossified at P0

absent mandibular angle ( J:254756 )

• at P0, the angular process is missing

absent mandibular condyloid process ( J:254756 )

• at P0, the condylar process is missing

absent mandibular coronoid process ( J:254756 )

• at P0, the coronoid process is missing

mandible hypoplasia ( J:254756 )

short mandible ( J:254756 )

• at E16.5, E18.5 and P0, the mandible is severely shortened

abnormal maxilla morphology ( J:254756 )

• newborns exhibit a hypoplastic and malformed maxilla

abnormal premaxilla morphology ( J:254756 )

• newborns exhibit a hypoplastic and malformed premaxilla

maxilla hypoplasia ( J:254756 )

short maxilla ( J:254756 )

• at E16.5, E18.5 and P0, the maxilla is severely shortened

domed cranium ( J:254756 )

• at P0, mice exhibit a domed skull

palate bone hypoplasia ( J:254756 )

• neonatal palatal bones are severely hypoplastic and thus palate is cleft

absent nasal capsule ( J:254756 )

• at P0, the nasal capsule is missing

abnormal nasal septum cartilage morphology ( J:254756 )

• at E17.5, the nasal septum cartilage is abnormally ossified and malformed

abnormal thyroid cartilage morphology ( J:254756 )

• thyroid cartilage is abnormally ossified at P0

abnormal bone ossification ( J:254756 )

• mice exhibit abnormal ossification within the maxilla and mandible, nasal septum, hyoid and laryngeal cartilages

premature bone ossification ( J:254756 )

• premature ossification in the body of hyoid bone is first seen at E15.5

premature metopic suture closure ( J:254756 )

• newborns exhibit premature frontal suture closure (craniosynostosis)

vision/eye

ocular hypertelorism ( J:254756 )

• at E14.5, embryos exhibit hypertelorism

hearing/vestibular/ear

abnormal tympanic ring morphology ( J:254756 )

• neonatal tympanic rings are thickened and deformed

nervous system

nervous system phenotype ( J:254756 )

N • morphology of cranial nerves is grossly normal at E10.5 and E12.5

abnormal sympathetic ganglion morphology ( J:254756 )

• size of sympathetic ganglia is reduced at E16.5 and E17.5

small dorsal root ganglion ( J:254756 )

• size of dorsal root ganglia is reduced at E16.5 and E17.5

digestive/alimentary system

palate bone hypoplasia ( J:254756 )

• neonatal palatal bones are severely hypoplastic and thus palate is cleft

palatal shelves fail to meet at midline ( J:254756 )

• palatal shelves are well developed and elevate to the horizontal position above tongue but fail to elongate or fuse at E14.5

• however, in vitro, palatal shelves show complete fusion with normal disappearance of the medial edge epithelium after 72 hours in organ culture

complete cleft palate ( J:254756 )

• newborns exhibit a complete cleft palate caused by craniofacial skeleton defects

abnormal tongue morphology ( J:254756 )

• at E16.5 and E18.5, the tongue is arched rather than flat

protruding tongue ( J:254756 )

• at E16.5, E18.5 and P0, mice exhibit an exposed (protuberant) tongue

growth/size/body

abnormal incisor morphology ( J:254756 )

• incisor tip is abnormally ossified at E14.5 and E15.5

palate bone hypoplasia ( J:254756 )

• neonatal palatal bones are severely hypoplastic and thus palate is cleft

absent nasal capsule ( J:254756 )

• at P0, the nasal capsule is missing

palatal shelves fail to meet at midline ( J:254756 )

• palatal shelves are well developed and elevate to the horizontal position above tongue but fail to elongate or fuse at E14.5

• however, in vitro, palatal shelves show complete fusion with normal disappearance of the medial edge epithelium after 72 hours in organ culture

round face ( J:254756 )

• at E14.5, embryos exhibit a round face

complete cleft palate ( J:254756 )

• newborns exhibit a complete cleft palate caused by craniofacial skeleton defects

abnormal tongue morphology ( J:254756 )

• at E16.5 and E18.5, the tongue is arched rather than flat

protruding tongue ( J:254756 )

• at E16.5, E18.5 and P0, mice exhibit an exposed (protuberant) tongue

abnormal nasal septum cartilage morphology ( J:254756 )

• at E17.5, the nasal septum cartilage is abnormally ossified and malformed

short snout ( J:254756 )

• at E14.5, embryos exhibit a short snout

cardiovascular system

cardiovascular system phenotype ( J:254756 )

N • morphology of the cardiac outflow tract and cardiac development is grossly normal at E17.5

embryo

embryo phenotype ( J:254756 )

N • both cranial neural crest cell (CNCC) migration and CNCC proliferation are normal

Genotype
MGI:7367354

cn5

• Allelic Composition: Gnas^tm5.1Lsw/Gnas^tm5.1Lsw; Tg(Nes-cre)1Atp/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

craniofacial

craniofacial phenotype ( J:254756 )

N • newborns exhibit normal craniofacial structures and completely fused palates; no cleft palate phenotype is observed

Genotype
MGI:5818291

cn6

• Allelic Composition: Gnas^tm5.1Lsw/Gnas^tm5.1Lsw; Tg(Slc5a2-cre)1Tauc/0
• Genetic Background: involves: C57BL/6 * DBA/2

homeostasis/metabolism

abnormal blood homeostasis ( J:233851 )

• the reduction of plasma phosphate 2 hours after parathyroid hormone injection is about 30% of that in controls, however this difference does not reach significance

• serum FGF23 is increased, although this is not statistically significant

increased circulating parathyroid hormone level ( J:233851 )

decreased circulating calcium level ( J:233851 )

• blood ionized calcium is reduced

• however, serum phosphate and index of fractional phosphate excretion is similar to controls

decreased vitamin D level ( J:233851 )

♂ • males show a reduction in serum 1,25-dihydroxyvitamin D levels

abnormal urine homeostasis ( J:233851 )

• parathyroid hormone-induced urinary cAMP excretion is significantly blunted

renal/urinary system

abnormal urine homeostasis ( J:233851 )

• parathyroid hormone-induced urinary cAMP excretion is significantly blunted

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pseudohypoparathyroidism		DOID:4184	OMIM:612462	J:233851

Genotype
MGI:6102945

cn7

• Allelic Composition: Gnas^tm5.1Lsw/Gnas^tm5.1Lsw; Tg(Fabp4-cre)1Abel/0
• Genetic Background: involves: FVB

muscle

decreased skeletal muscle triglyceride level ( J:159612 )

mortality/aging

premature death ( J:159612 )

• by 14 weeks in severely affected mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:159612 )

N • surviving mice exhibit normal food intake, energy expenditure and respiratory ratio at ambient or cold temperatures

N • mice exhibit normal T4 levels

increased fatty acid oxidation ( J:159612 )

• in the muscle of mice fed a high-fat diet

impaired adaptive thermogenesis ( J:159612 )

• in response to cold exposure on a high fat diet, mice exhibit reduced body temperature and a 3-fold increase in energy expenditure compared with control mice

hypoglycemia ( J:159612 )

• under basal fed conditions

increased circulating corticosterone level ( J:159612 )

decreased circulating insulin level ( J:159612 )

• under basal fed conditions

decreased circulating leptin level ( J:159612 )

• at 3 months in surviving mice

• however, adiponectin levels are normal

decreased circulating free fatty acids level ( J:159612 )

decreased circulating triglyceride level ( J:159612 )

abnormal urine catecholamine level ( J:159612 )

• increased norephinephrine excretion

increased energy expenditure ( J:159612 )

• 3-fold in response to cold exposure on a high fat diet

decreased susceptibility to diet-induced obesity ( J:159612 )

• when fed a high-fat diet

improved glucose tolerance ( J:159612 )

increased insulin sensitivity ( J:159612 )

decreased liver triglyceride level ( J:159612 )

decreased skeletal muscle triglyceride level ( J:159612 )

adipose tissue

decreased subcutaneous adipose tissue amount ( J:159612 )

• almost completely absent in severely affected mice

decreased white adipose tissue amount ( J:159612 )

• at 3 months in surviving mice

• however, no macrophage infiltration is observed

abnormal adipose tissue development ( J:159612 )

• embryonic cells exhibit reduced adipogenesis compared with control cells

decreased body fat mass ( J:159612 )

• at 3 months in surviving mice

• however, weights of brown adipose tissue, liver, kidney and heart are normal

decreased white fat cell size ( J:159612 )

• in epididymal WAT

decreased epididymal fat pad weight ( J:159612 )

• almost completely absent in severely affected mice

decreased inguinal fat pad weight ( J:159612 )

• almost completely absent in severely affected mice

decreased mesenteric fat pad weight ( J:159612 )

• almost completely absent in severely affected mice

decreased renal fat pad weight ( J:159612 )

• almost completely absent in severely affected mice

abnormal white adipose tissue physiology ( J:159612 )

• isoproterenol-treated white adipose tissue adipocytes exhibit reduced lipolytic response compared with control cells

growth/size/body

decreased body fat mass ( J:159612 )

• at 3 months in surviving mice

• however, weights of brown adipose tissue, liver, kidney and heart are normal

increased lean body mass ( J:159612 )

• at 3 months in surviving mice

decreased susceptibility to diet-induced obesity ( J:159612 )

• when fed a high-fat diet

decreased body size ( J:159612 )

• in severely affected mice

decreased body weight ( J:159612 )

• at 3 months in surviving mice

• however, weights of brown adipose tissue, liver, kidney and heart are normal

decreased body length ( J:159612 )

• at 3 months in surviving mice

behavior/neurological

decreased locomotor activity ( J:159612 )

• in cold-exposed mice

liver/biliary system

decreased liver triglyceride level ( J:159612 )

renal/urinary system

abnormal urine catecholamine level ( J:159612 )

• increased norephinephrine excretion

integument

decreased subcutaneous adipose tissue amount ( J:159612 )

• almost completely absent in severely affected mice

cellular

increased fatty acid oxidation ( J:159612 )

• in the muscle of mice fed a high-fat diet