Phenotypes associated with this allele

• Allele Symbol: Hprt1^tm1Detl
• Allele Name: targeted mutation 1, Peter J Detloff
• Allele ID: MGI:1861939
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hprt1^tm1Detl/Hprt1^tm1Detl	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:2178749
ot2	Hprt1^tm1Detl/Y	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:2178750

Genotype
MGI:2178749

hm1

• Allelic Composition: Hprt1^tm1Detl/Hprt1^tm1Detl
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

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

mortality/aging

premature death ( J:44728 )

♀ • median age of death of mutants is 45 weeks, with all animals dying by 53 weeks

behavior/neurological

decreased exploration in new environment ( J:44728 )

♀ • after 18 weeks of age, mutants have lower exploratory activity in cages when lid and food rack are removed

abnormal motor capabilities/coordination/movement ( J:44728 )

♀ • when suspended by tail, mice tend to escape by climbing up experimenter's fingers, but by 18 weeks of age, mutants have lost this ability

limb grasping ( J:44728 )

♀ • many mutants display limb clasping upon tail suspension; clasping is involuntary and tends to be more frequent in older mice

♀ • when lowered into cage, limbs remain clasped rather than being outstretched as observed in controls; impairment increases with age of mutant

tremors ( J:44728 )

♀ • mice at 44-48 weeks display a slight resting tremor, preceding ataxia

ataxia ( J:44728 )

♀ • me mice aged between 44 and 48 weeks exhibit slight ataxia characterized by a swaying gait

♀ • onset of ataxia is typically followed by death within 3-6 days

impaired coordination ( J:44728 )

♀ • older mutants (>18 weeks) tend to fall off rod in rotarod paradigm to larger extent than younger mutants or age-matched controls; impairment increases with age of mutant

jerky movement ( J:44728 )

♀ • mice observed at 44-48 weeks showed frequent jerks of the body

abnormal gait ( J:44728 )

♀ • some mice have a swaying gait, after onset of ataxia

decreased vertical activity ( J:44728 )

♀ • mutant mice exhibit progressively less vertical activity as they age

seizures ( J:44728 )

♀ • some older mice (>18 weeks of age) display seizures but mice younger than 18 weeks do not exhibit seizure activity

♀ • 7 mice were assayed to determine penetrance of seizure susceptibility; 4/7 experienced at least one seizure by 21 weeks of age, and all 7 had at least one seizure by 35 weeks

convulsive seizures ( J:44728 )

♀ • handling of mice sometimes causes a convulsive episode; seizures on average started ~36 seconds after suspension by the tail and last ~42 seconds

nervous system

seizures ( J:44728 )

♀ • some older mice (>18 weeks of age) display seizures but mice younger than 18 weeks do not exhibit seizure activity

♀ • 7 mice were assayed to determine penetrance of seizure susceptibility; 4/7 experienced at least one seizure by 21 weeks of age, and all 7 had at least one seizure by 35 weeks

convulsive seizures ( J:44728 )

♀ • handling of mice sometimes causes a convulsive episode; seizures on average started ~36 seconds after suspension by the tail and last ~42 seconds

abnormal brain morphology ( J:44728 )

♀ • in brains of affected mice aged 30-46 weeks, a densely staining (with Hprt antibody) mass in nuclei in many neurons, but this is never observed in control animals

♀ • brain size/weight is normal compared to controls

neuronal intranuclear inclusions ( J:44728 )

♀ • neuronal intranuclear inclusions (NIIs) are seen in many neurons in many brain regions; most neurons only contain 1 NII

♀ • ~30% of neurons in pyramidal layer of cerebral cortex contain an NII, while only 6% of neurons in deeper layers contain them

liver/biliary system

hepatic steatosis ( J:44728 )

♀ • mice (2/2 females examined between 34 and 38 weeks) exhibit moderately fatty livers

Genotype
MGI:2178750

ot2

• Allelic Composition: Hprt1^tm1Detl/Y
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

mortality/aging

premature death ( J:44728 )

♂ • median age of death of mutants is 45 weeks, with all animals dying by 53 weeks

growth/size/body

increased body weight ( J:44728 )

♂ • at 23 weeks, males weigh more than age-matched WT male controls

behavior/neurological

decreased exploration in new environment ( J:44728 )

♂ • after 18 weeks of age, mutants have lower exploratory activity in cages when lid and food rack are removed

abnormal motor capabilities/coordination/movement ( J:44728 )

♂ • when suspended by tail, mice tend to escape by climbing up experimenter's fingers, but by 18 weeks of age, mutants have lost this ability

limb grasping ( J:44728 )

♂ • many mutants display limb clasping upon tail suspension; clasping is involuntary and tends to be more frequent in older mice

♂ • when lowered into cage, limbs remain clasped rather than being outstretched as observed in controls; impairment increases with age of mutant

tremors ( J:44728 )

♂ • some mice at 44-48 weeks display a slight resting tremor, preceding ataxia

ataxia ( J:44728 )

♂ • some mice aged between 44 and 48 weeks exhibit slight ataxia characterized by a swaying gait

♂ • onset of ataxia is typically followed by death within 3-6 days

impaired coordination ( J:44728 )

♂ • older mutants (>18 weeks) tend to fall off rod in rotarod paradigm to greater extent than younger mutants or age-matched controls; impairment increases with age of mutant

jerky movement ( J:44728 )

♂ • mice observed at 44-48 weeks showed frequent jerks of the body

abnormal gait ( J:44728 )

♂ • some mice have a swaying gait, with development of ataxia

decreased vertical activity ( J:44728 )

♂ • mutant mice exhibit progressively less vertical activity as they age

seizures ( J:44728 )

♂ • some older mice (>18 weeks of age) display seizures but mice younger than 18 weeks do not exhibit seizure activity

♂ • 7 mice were assayed to determine penetrance of seizure susceptibility; 4/7 experienced at least one seizure by 21 weeks of age, and all 7 had at least one seizure by 35 weeks

convulsive seizures ( J:44728 )

♂ • handling of mice sometimes causes a convulsive episode; seizures on average started ~36 seconds after suspension by the tail and last ~42 seconds

nervous system

seizures ( J:44728 )

♂ • some older mice (>18 weeks of age) display seizures but mice younger than 18 weeks do not exhibit seizure activity

♂ • 7 mice were assayed to determine penetrance of seizure susceptibility; 4/7 experienced at least one seizure by 21 weeks of age, and all 7 had at least one seizure by 35 weeks

convulsive seizures ( J:44728 )

♂ • handling of mice sometimes causes a convulsive episode; seizures on average started ~36 seconds after suspension by the tail and last ~42 seconds

abnormal brain morphology ( J:44728 )

♂ • in brains of affected mice aged 30-46 weeks, a densely staining (with Hprt antibody) mass in nuclei in many neurons, but this is never observed in control animals

♂ • brain size/weight is normal compared to controls

neuronal intranuclear inclusions ( J:44728 )

♂ • neuronal intranuclear inclusions (NIIs) are seen in many neurons in many brain regions; most neurons only contain 1 NII

♂ • ~30% of neurons in pyramidal layer of cerebral cortex contain an NII, while only 6% of neurons in deeper layers contain them

reproductive system

testicular atrophy ( J:44728 )

♂ • 1/2 males at 34-38 weeks displayed complete testicular atrophy but other male was normal

liver/biliary system

hepatic steatosis ( J:44728 )

♂ • mice (2/2 males examined between 34 and 38 weeks) exhibit moderately fatty livers

endocrine/exocrine glands

testicular atrophy ( J:44728 )

♂ • 1/2 males at 34-38 weeks displayed complete testicular atrophy but other male was normal