Phenotypes associated with this allele

• Allele Symbol: Gnas^tm4Lsw
• Allele Name: targeted mutation 4, Lee S Weinstein
• Allele ID: MGI:3582306
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gnas^tm4Lsw/Gnas^tm4Lsw	involves: 129S6/SvEvTac * Black Swiss * CD-1	MGI:3583676
ht2	Gnas^tm4Lsw/Gnas^+	involves: 129S6/SvEvTac	MGI:5818292
ht3	Gnas^tm4Lsw/Gnas^+	involves: 129S6/SvEvTac * Black Swiss * CD-1	MGI:3583677

Genotype
MGI:3583676

hm1

• Allelic Composition: Gnas^tm4Lsw/Gnas^tm4Lsw
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss * CD-1

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

mortality/aging

prenatal lethality ( J:99237 )

Genotype
MGI:5818292

ht2

• Allelic Composition: Gnas^tm4Lsw/Gnas⁺
• Genetic Background: involves: 129S6/SvEvTac

homeostasis/metabolism

abnormal blood homeostasis ( J:233851 )

• mice with a maternally inherited allele exhibit higher levels of serum FGF23

renal/urinary system

abnormal kidney morphology ( J:233851 )

• mice with a maternally inherited allele exhibit higher renal Cyp24a1 mRNA but not Cyp27b1 mRNA

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Albright's hereditary osteodystrophy		DOID:0080053	OMIM:103580	J:233851

Genotype
MGI:3583677

ht3

• Allelic Composition: Gnas^tm4Lsw/Gnas⁺
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss * CD-1

mortality/aging

postnatal lethality, incomplete penetrance ( J:99237 )

• when the allele is maternally inherited, about 50% of heterozygotes die before 3 weeks of age, mostly in the first 3 days after birth

homeostasis/metabolism

increased circulating leptin level ( J:99237 )

• when the allele is maternally inherited, serum leptin levels are 3-fold and more than 2-fold higher compared to wild-type and heterozygotes with a paternally inherited allele, respectively

• however, when the allele is paternally inherited, serum leptin levels are still increased compared to wild-type

increased circulating triglyceride level ( J:99237 )

• serum triglyceride levels are increased in heterozygotes with a maternally inherited allele compared to those with a paternally inherited allele

edema ( J:99237 )

• when the allele is maternally inherited, subcutaneous edema is present at birth but resolves by 1-2 days of age

decreased oxygen consumption ( J:99237 )

• when the allele is maternally inherited but not when it is paternally inherited, resting metabolism is significantly lower at 23 and 30 degrees C; however, serum TSH and free thyroxine levels are normal suggesting that thyroid function is not impaired

abnormal glucose homeostasis ( J:99237 )

increased circulating glucose level ( J:99237 )

• serum glucose levels are increased in heterozygotes with a maternally inherited allele compared to those with a paternally inherited allele

increased circulating insulin level ( J:99237 )

• when the allele is paternally inherited, serum insulin but not serum glucose levels are elevated compared to wild-type mice

• serum insulin levels are increased in heterozygotes with a maternally inherited allele compared to levels in heterozygotes with a paternally inherited allele

impaired glucose tolerance ( J:99237 )

• glucose tolerance is impaired in random-fed mice when the allele is maternally or paternally inherited

insulin resistance ( J:99237 )

• insulin resistance is seen when the allele is maternally or paternally inherited, although the insulin resistance is more severe when the allele is maternally inherited

adipose tissue

abnormal adipose tissue morphology ( J:99237 )

• when the allele is maternally inherited, increased lipid accumulation is seen in the white and brown fat

increased brown adipose tissue amount ( J:99237 )

• when the allele is paternally inherited, total body weight is normal but the brown fat weight is increased

increased white adipose tissue amount ( J:99237 )

• when the allele is paternally inherited, total body weight is normal but the white fat pad weight is increased

increased total body fat amount ( J:99237 )

• when the allele is maternally inherited, fat mass is increased about 2-fold

increased interscapular fat pad weight ( J:99237 )

• when the allele is paternally inherited, greater lipid accumulation is seen in both the brown and white fat in the interscapular fat pad

growth/size/body

obese ( J:99237 )

• when the allele is maternally inherited, body weight is increased by about 20%; however, when the allele is paternally inherited, body weight is not significantly different from wild-type

cellular

paternal imprinting ( J:99237 )

• heterozygotes inheriting the allele from the mother display a more severe phenotype