Phenotypes associated with this allele

• Allele Symbol: Magel2^tm1Stw
• Allele Name: targeted mutation 1, Colin L Stewart
• Allele ID: MGI:3760092
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Magel2^tm1Stw/Magel2^tm1Stw	C57BL/6-Magel2^tm1Stw	MGI:3760114
hm2	Magel2^tm1Stw/Magel2^tm1Stw	C57BL/6-Magel2^tm1Stw/J	MGI:5781308
ht3	Magel2^tm1Stw/Magel2^+	C57BL/6-Magel2^tm1Stw	MGI:3834842

Genotype
MGI:3760114

hm1

• Allelic Composition: Magel2^tm1Stw/Magel2^tm1Stw
• Genetic Background: C57BL/6-Magel2^tm1Stw

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:125637 )

• when the Magel2^tm1Stw allele is inherited paternally, 10% fewer mice survive to weaning than expected

reproductive system

reduced male fertility ( J:125637 )

♂ • when the Magel2^tm1Stw allele is inherited paternally, males reproduce but with decreasing frequency and cease mating by 16 weeks unlike wild-type mice

♂ • however, no defects in spermatogenesis and testes weight are observed

behavior/neurological

decreased compensatory feeding amount ( J:125637 )

• when the Magel2^tm1Stw allele is inherited paternally, after 24 hours starvation mice consume less food than wild-type mice

decreased locomotor activity ( J:125637 )

• when the Magel2^tm1Stw allele is inherited paternally, mice run significantly less than wild-type mice (3047+/-930 counts per day compared to 12770+/-2343 counts per day for wild-type mice)

• when the Magel2^tm1Stw allele is inherited paternally, mice run in more frequent and shorter bouts (8.5+/-0.7 bouts per day compared to 4.9+/-0.4 bouts per day for wild-type mice and 21.8+/-4.3 minutes per bout compared to 83.1+/-15.4 minutes per bout for wild-type mice)

abnormal circadian behavior ( J:125637 )

• when the Magel2^tm1Stw allele is inherited paternally, rhythms have lower chi-squared periodogram amplitudes than in wild-type mice

abnormal locomotor circadian rhythm ( J:125637 )

• when the Magel2^tm1Stw allele is inherited paternally, mice run significantly less than wild-type mice (3047+/-930 counts per day compared to 12770+/-2343 counts per day for wild-type mice)

• when the Magel2^tm1Stw allele is inherited paternally, mice run in more frequent and shorter bouts (8.5+/-0.7 bouts per day compared to 4.9+/-0.4 bouts per day for wild-type mice and 21.8+/-4.3 minutes per bout compared to 83.1+/-15.4 minutes per bout for wild-type mice)

• when the Magel2^tm1Stw allele is inherited paternally, mice exhibit less daily activity during the subjective night (76.9+/-2.8% compared to 86.6+/-2.5% for wild-type mice)when the Magel2^tm1Stw allele is inherited paternally, mice exhibit less daily activity during the subjective night (76.9+/-2.8% compared to 86.6+/-2.5% for wild-type mice)

growth/size/body

growth/size/body region phenotype ( J:125637 )

N • when the Magel2^tm1Stw allele is inherited paternally, surviving mice display no abnormalities in size or weight up to 2 years of age

cellular

maternal imprinting ( J:125637 )

• only the paternally inherited allele is expressed

Genotype
MGI:5781308

hm2

• Allelic Composition: Magel2^tm1Stw/Magel2^tm1Stw
• Genetic Background: C57BL/6-Magel2^tm1Stw/J

adipose tissue

increased body fat mass ( J:233299 )

behavior/neurological

decreased grip strength ( J:233299 )

• hindlimb and forelimb grip strength is less than controls and declines with age

decreased vertical activity ( J:233299 )

• less vertical activity in light (42%) and dark (55%) cycles as compared to controls

decreased locomotor activity ( J:233299 )

• total distance travelled on progressive treadmill test is decreased as compared to controls in female mice and older male mice, 14 week old male mice perform similar to controls

cellular

abnormal autophagy ( J:233299 )

• altered autophagy in soleus muscle

• p62 levels in fed mice are higher than in fed controls, fasted levels are similar to control

growth/size/body

increased body fat mass ( J:233299 )

decreased lean body mass ( J:233299 )

obese ( J:233299 )

• both male and female mice are obese with more fat mass and less lean mass than controls

• body composition in females is more abnormal than in males and consists of 2.3 times more fat and 8% less lean mass than controls

mortality/aging

prenatal lethality, incomplete penetrance ( J:233299 )

• increased prenatal mortality as compared to controls

• early failure to thrive is observed

muscle

decreased skeletal muscle fiber size ( J:233299 )

• smaller muscle fibers in gastrocnemius

• fiber type redistribution is not observed

increased skeletal muscle fiber size ( J:233299 )

• larger muscle fibers in soleus as compared to control

• fiber type redistribution is not observed

decreased skeletal muscle weight ( J:233299 )

• reduction of total limb muscle weight to 87-93% of controls

• all individual muscle groups (gastrocnemius-soleus-plantaris, quadriceps, and tibialis anterior) are lighter than controls

skeletal muscle atrophy ( J:233299 )

respiratory system

respiratory system phenotype ( J:233299 )

N • respiratory deficiency is not observed in young mice (P2 and P18)

skeleton

scoliosis ( J:233299 )

• mild spinal curvature characterized by a upward rotation of the right aspect of skull and, in some mice, a right thoracic curve

homeostasis/metabolism

abnormal autophagy ( J:233299 )

• altered autophagy in soleus muscle

• p62 levels in fed mice are higher than in fed controls, fasted levels are similar to control

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Prader-Willi syndrome		DOID:11983	OMIM:176270	J:233299

Genotype
MGI:3834842

ht3

• Allelic Composition: Magel2^tm1Stw/Magel2⁺
• Genetic Background: C57BL/6-Magel2^tm1Stw

Older Magel2^tm1Stw/Magel2⁺ females that inherit the mutant allele paternally lack corpora lutea in the ovaries

mortality/aging

postnatal lethality, incomplete penetrance ( J:144836 )

• only 50-60% of pups born to female mice that inherit the mutant allele paternally survive until weaning

early reproductive senescence ( J:144836 )

• infertility occurs in both sexes by 24 weeks of age in mice that inherit the mutant allele paternally

• fertility rates are normal between 7-14 weeks of age, drops to about 20% at 19-24 weeks of age, with no litters are born after 24 weeks of age

• at younger ages, there is also a significant increase in the mean time between pairing and successful breeding (males: 9 days vs. 4 days for controls, females: 12 days vs. 4 days in controls)

cellular

maternal imprinting ( J:144836 )

• only the paternally inherited allele is expressed

reproductive system

abnormal corpus luteum morphology ( J:144836 )

♀ • an absence of corpus lutea is noted in 10 of 14 female mice that are over 24 weeks of age and have inherited the mutant allele paternally

early reproductive senescence ( J:144836 )

• infertility occurs in both sexes by 24 weeks of age in mice that inherit the mutant allele paternally

• fertility rates are normal between 7-14 weeks of age, drops to about 20% at 19-24 weeks of age, with no litters are born after 24 weeks of age

• at younger ages, there is also a significant increase in the mean time between pairing and successful breeding (males: 9 days vs. 4 days for controls, females: 12 days vs. 4 days in controls)

delayed vaginal opening ( J:144836 )

• in female mice inheriting the mutant allele paternally, vaginal opening is significantly delayed by 1.4 days

delayed estrous cycle ( J:144836 )

• in female mice inheriting the mutant allele paternally, the age of first estrus is delayed by 5.3 days

abnormal proestrus ( J:144836 )

♀ • only 25% of mice experience proestrus in female mice that are 26 weeks of age and have inherited the mutant allele paternally

prolonged estrous cycle ( J:144836 )

♀ • estrous cycle is prolonged and irregular in female mice that have inherited the mutant allele paternally

decreased litter size ( J:144836 )

• a mean of 6.4 pups is born to female mice that inherit the mutant allele paternally compared to 7.8 pups for controls

taste/olfaction

impaired olfaction ( J:144836 )

• latency time to find buried food is more than twice that of controls for mice that are over 24 weeks of age and have inherited the mutant allele paternally

• fasted male mice that have inherited the mutant allele paternally only investigate a dried vanilla spot for 0.75 s compared to 6.7 s for controls

• sexually-experienced male mice that have inherited the mutant allele paternally show no preference for female soiled bedding unlike their wild-type controls

behavior/neurological

pup cannibalization ( J:144836 )

♀ • female mice with paternal inheritance of the mutant allele frequently cannibalize their pups

endocrine/exocrine glands

abnormal corpus luteum morphology ( J:144836 )

♀ • an absence of corpus lutea is noted in 10 of 14 female mice that are over 24 weeks of age and have inherited the mutant allele paternally

homeostasis/metabolism

decreased circulating testosterone level ( J:144836 )

• mean serum testosterone levels are significantly lower in male mice that inherit the mutant allele paternally (6.1 ng/ml versus 20.2 ng/ml in controls)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Prader-Willi syndrome		DOID:11983	OMIM:176270	J:144836