Hprt1<tm1Detl> Targeted Allele Detail MGI Mouse (MGI:1861939)

Hprt1^tm1Detl
Targeted Allele Detail

Nomenclature

Symbol:	Hprt1^tm1Detl
Name:	hypoxanthine guanine phosphoribosyl transferase 1; targeted mutation 1, Peter J Detloff
MGI ID:	MGI:1861939
Synonyms:	hprt^(CAG)146, JO1
Gene:	Hprt1 Location: ChrX:50341314-50374836 bp, + strand Genetic Position: ChrX, 17.0 cM, cytoband A6

Mutation
origin

Germline Transmission:	Earliest citation of germline transmission: J:44728
Parent Cell Line:	R1 (ES Cell)
Strain of Origin:	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺

Mutation
description

Allele Type:	Targeted (knock-in)
Mutation:	Insertion
	A construct was created that introduced a long CAG repeat (n=146 units) into an Xho1 site in exon 3 of a genomic fragment of the locus. An additional 4.9kb genomic fragment, which included exon 4 of the gene, was added to this repeat-containing construct. Appropriately targeted clones had sequences containing the 146-unit CAG repeat, encoding a stretch of 146 glutamines, in place of wild-type exon 3. (J:44728)

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:	Mouse Strains: 1 strain available Cell Lines: 0 lines available
Carrying any Hprt1 Mutation:	19 strains or lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	hm1	ot2
behavior/neurological		√	√
decreased exploration in new environment		√	√
abnormal motor capabilities/coordination/movement		√	√
abnormal involuntary movement		√	√
limb grasping		√	√
tremors		√	√
ataxia		√	√
impaired coordination		√	√
decreased vertical activity		√	√
abnormal gait		√	√
seizures		√	√
convulsive seizures		√	√
		hm1	ot2
endocrine/exocrine glands			√
testicular atrophy			√
		hm1	ot2
growth/size			√
increased body weight			√
		hm1	ot2
life span/aging		√	√
premature death		√	√
		hm1	ot2
liver/biliary system		√	√
hepatic steatosis		√	√
		hm1	ot2
nervous system		√	√
seizures		√	√
convulsive seizures		√	√
abnormal brain morphology		√	√
neuronal intranuclear inclusions		√	√
		hm1	ot2
reproductive system			√
testicular atrophy			√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
hm1	Hprt1^tm1Detl/Hprt1^tm1Detl	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
life span/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 abnormal involuntary movement (J:44728) mice observed at 44-48 weeks showed frequent jerks of the body 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 decreased vertical activity (J:44728) mutant mice exhibit progressively less vertical activity as they age abnormal gait (J:44728) some mice have a swaying gait, after onset of ataxia 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	Allelic Composition	Genetic Background
ot2	Hprt1^tm1Detl/Y	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
life span/aging premature death (J:44728) median age of death of mutants is 45 weeks, with all animals dying by 53 weeks growth/size 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 abnormal involuntary movement (J:44728) mice observed at 44-48 weeks showed frequent jerks of the body 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 decreased vertical activity (J:44728) mutant mice exhibit progressively less vertical activity as they age abnormal gait (J:44728) some mice have a swaying gait, with development of ataxia 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 endocrine/exocrine glands 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

References

Original:	J:44728 Ordway JM et al., "Ectopically expressed CAG repeats cause intranuclear inclusions and a progressive late onset neurological phenotype in the mouse." Cell 1997 Dec 12;91(6):753-63
All:	4 reference(s)

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