Overview

Also Known As: PS1-

These Psen1 knock-out mice exhibit a drastic reduction in neural progenitor cells in the embryo with death occuring minutes after being born.

Donating Investigator

Jie Shen, Harvard Med Sch/Brigham Women's Hosp

Genetic overview

Genetic Background	Generation

Psen1^tm1Shn

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Psen1	presenilin 1

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Research Applications

Developmental Biology Research
Neurobiology Research
Mouse/Human Gene Homologs

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Presenilin-1 is the major gene responsible for early-onset familial Alzheimer's disease. Mice that are homozygous null for this gene die within minutes after being born. Externally, mice exhibit shortened tails that curve to the right, thickened necks, loose skin and hind limbs that curve towards the midline. Their weight is 15-20% that of wildtype. Gross skeletal malformations and central nervous system abnormalities are observed. Death presumably results from impaired respiratory mechanics due to ribcage deformities. Histological examination indicates that alveoli are marginally expanded. By embryonic day 9.5, there is a drastic reduction in neural progenitor cells. Later, the brain exhibits hemorrhages and symmetric cerebral cavitation. Cavitation occurs primarily in the ventrolateral region of the ventricular zone in the posterior portion of the brain.

Development

A targeting construct containing a neomycin cassette was electroporated into ES cells. The construct was designed to disrupt exons 2 and 3. ES cells were injected into C57BL/6 blastocysts. Resulting animals generate aberrant mRNA splice products, but no protein is detected.

Control Suggestions

Wild-type from the colony

Additional Information

Considerations for Choosing Controls

Selected References

Shen J; Bronson RT; Chen DF; Xia W; Selkoe DJ; Tonegawa S. 1997. Skeletal and CNS defects in Presenilin-1-deficient mice. Cell 89(4):629-39PubMed: 9160754 MGI: J:40365

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Genetics

Psen1^tm1Shn

Allele Symbol: Psen1^tm1Shn

Allele Name	targeted mutation 1, Jie Shen
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Psen1^tm1Shn; targeted mutation 1, Jie Shen
Gene Symbol and Name	Psen1, presenilin 1
Gene Synonym(s)	alzheimer disease 3 homolog; S182; Ad3h; AD3; Ad3h; presenilin-1; PS-1; PS1; FAD; ACNINV3
Strain of Origin	129S7/SvEvBrd-Hprt^b-m2
Chromosome	12
Molecular Note	Exon 3 of the Psen1 gene, encoding the translation initiation codon, was deleted and replaced with a neomycin cassette. Northern blots of brain tissue from homozygous mutant mice showed a small amount of mutant Psen1 mRNA, smaller in size than wild-type Psen1. IP-Western blotting detected no C-terminal protein fragment in homozygous mutant mice. The authors conclude that this mutant is a null allele.
Mutations Made By	Jie Shen, Harvard Med Sch/Brigham Women's Hosp

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Alzheimer's disease 3

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Alzheimer's disease

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Genotype: Psen1^tm1Shn related

Developmental Biology Research
- Postnatal Lethality
  - Homozygous
- Neurodevelopmental Defects
- Skeletal Defects
Neurobiology Research
- Alzheimer's Disease
- Behavioral and Learning Defects
- Neurodegeneration
- Neurodevelopmental Defects
Mouse/Human Gene Homologs
- Alzheimer's

Neurobiology Research
- Alzheimer's Disease
  - Presenilin mutants

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Psen1^tm1Shn/Psen1^tm1Shn
Not Specified

cellular phenotype

abnormal apoptosis
- at E10 the total number of apoptotic cells and relative percentage of apoptotic cells to progenitor cells in the forebrain-midbrain junction is reduced about 50% compared to littermate controls

Genotype: Psen1^tm1Shn/Psen1^tm1Shn
involves: 129S7/SvEvBrd * C57BL/6

cardiovascular system phenotype

intracranial hemorrhage
- intracranial hemorrhage with varying degrees of severity and time of onset that can appear as early as E12.5

limbs/digits/tail phenotype

abnormal hindlimb morphology
- hindlimbs are curved toward the midline

curly tail
- tails are curled toward the right side of the body

kinked tail
- by E12.5, all mutants display a kinked tail

short tail

mortality/aging

neonatal lethality, complete penetrance
- none survive for longer than 30 min after natural birth or C-section

nervous system phenotype

abnormal brain morphology
- the brain shows symmetric cavitation in the ventrolateral region of the ventricular zone in the posterior portion of the brain at E17.5

abnormal cerebral cortex morphology
- at the level of the interventricular foramen of Monroe, where the lateral ventricles join the third ventricle, a disruption of the cerebral architecture is seen at E16.5

abnormal dentate gyrus morphology
- dentate gyrus is less distinct than in controls at E17.5

abnormal diencephalon morphology
- the ependymal layer and the ventricular zone at the diencephalic sulcus are disrupted

abnormal hippocampus development
- hippocampal formation is hardly recognizable at E14.5, whereas in controls it is quite prominent

abnormal lateral ganglionic eminence morphology
- fewer dividing progenitor cells in the luminal layer of the ventricular zone in the lateral ganglionic eminence, resulting in a thinner ventricular zone
- the lateral ganglionic eminence is much less prominent starting at E12.5 than in controls

abnormal neuron differentiation

abnormal temporal lobe morphology
- atrophy in the subcortical region of the temporal lobe along the external capsule in the brain

abnormal third ventricle morphology
- the ventricular zone along the mid-portions of the third ventricle is absent in E14.5 mutants

decreased neuronal precursor cell number
- the ventricular and subventricular zones in the ventrolateral region show severe loss of neural progenitor cells leading to symmetric cavitation at E17.5

dilated lateral ventricles

intracranial hemorrhage
- intracranial hemorrhage with varying degrees of severity and time of onset that can appear as early as E12.5

neuron degeneration
- exhibit a progression of neuronal loss from anterior to posterior portions of the cerebral hemispheres
- region-specific (the ventricular and subventricular zones in the ventrolateral region of the brain and subcortical region of the temporal lobe) symmetric loss of neurons and neural progenitor cells with varying severity at E17.5-18.5 and in neonates

small embryonic telencephalon
- smaller at E9.5

thin cortical plate

cellular phenotype

abnormal neuron differentiation

craniofacial phenotype

occipital bone hypoplasia
- occipital bones are underdeveloped

respiratory system phenotype

abnormal pulmonary alveolus morphology
- the alveoli are poorly expanded, probably due to mechanical difficulties imposed by the malformed ribcage

skeleton phenotype

abnormal axial skeleton morphology
- axial skeleton is severely malformed
- caudal to the pelvis, the axial skeletal structure is completely missing

abnormal bone ossification
- axial skeleton has about 12 pairs of underossified bones and 3-4 pairs or random ossification centers followed by an unossified and unsegmented cartilaginous mass on the dorsal aspect of the vertebral column

abnormal costovertebral joint morphology
- the ribs are detached from the vertebral column and are only present in the thoracic region in association with the underossified bones in the vertebral column

abnormal rib morphology
- the posterior rib segments are missing and the existing ribs are underossified and fused

abnormal spine curvature
- lack the normal cervical and lumbar flexures of the vertebral column

abnormal sternum morphology
- sternum is shorter, thicker and lacks intersternebral cartilage

cervical vertebral fusion

decreased rib number
- homozygotes have only 9-11 instead of 13 pairs of ribs

lumbar vertebral fusion

occipital bone hypoplasia
- occipital bones are underdeveloped

rib fusion
- existing ribs are fused

sacral vertebral fusion

short sternum

vertebral fusion

embryo phenotype

abnormal rostral-caudal patterning of the somites
- the segmentation in the caudal region of the somites appears less distinct at E9.5-10.5

short rostral-caudal axis
- shorter rostro-caudal body axes

growth/size/body region phenotype

abnormal postnatal growth/weight/body size
- thick neck

decreased body length

decreased body weight
- neonates weigh 15-20% less than control littermates

integument phenotype

loose skin

References

Shen J; Bronson RT; Chen DF; Xia W; Selkoe DJ; Tonegawa S. 1997. Skeletal and CNS defects in Presenilin-1-deficient mice. Cell 89(4):629-39PubMed: 9160754 MGI: J:40365

Additional - Psen1^tm1Shn related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Psen1^tm1Shn
- Genotyping resources and troubleshooting
Breeding Considerations

Homozygotes die within minutes after being born. The expected coat color is black.
- Additional Breeding and Husbandry Support
Citation
When using the PS1- mouse strain in a publication, please cite the originating article(s) and include JAX stock #003615 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or wildtype for Psen1<tm1Shn>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

Related Products and Services

Frozen Mouse Embryo	B6.129-Psen1<tm1Shn>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129-Psen1<tm1Shn>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129-Psen1<tm1Shn>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129-Psen1<tm1Shn>/J Frozen Embryo	$3373.50

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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Also Known As: PS1-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Psen1tm1Shn

Allele Symbol: Psen1tm1Shn

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Genotype: Psen1tm1Shn related

Mammalian Phenotype Terms by Genotype

Genotype: Psen1tm1Shn/Psen1tm1ShnNot Specified

cellular phenotype

Genotype: Psen1tm1Shn/Psen1tm1Shninvolves: 129S7/SvEvBrd * C57BL/6

cardiovascular system phenotype

limbs/digits/tail phenotype

mortality/aging

nervous system phenotype

cellular phenotype

craniofacial phenotype

respiratory system phenotype

skeleton phenotype

embryo phenotype

growth/size/body region phenotype

integument phenotype

References

Additional - Psen1tm1Shn related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Psen1^tm1Shn

Allele Symbol: Psen1^tm1Shn

Genotype: Psen1^tm1Shn related

Genotype: Psen1^tm1Shn/Psen1^tm1Shn
Not Specified

Genotype: Psen1^tm1Shn/Psen1^tm1Shn
involves: 129S7/SvEvBrd * C57BL/6

Additional - Psen1^tm1Shn related