Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain C57BL/6 Generation N6+4pN1   Donating Investigator Jie Shen,   Harvard Med Sch/ Brigham Women's Hosp

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 Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying   Psen1^tm1Shn allele

003822

B6;129S-Psen1tm1Shn/J

View Strains carrying   Psen1^tm1Shn     (1 strain)

Strains carrying other alleles of Psen1

004193	B6.129-Psen1tm1Mpm/J
007685	B6.129P2-Psen1tm1Vln/J
004807	B6.Cg-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/J
007605	B6;129P-Psen1tm1Vln/J

View Strains carrying other alleles of Psen1     (4 strains)

Additional Web Information

Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

	Alzheimer Disease 3 - Models with phenotypic similarity to human disease where etiologies involve orthologs.1
	Alzheimer Disease; AD - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Psen1^tm1Shn/Psen1^tm1Shn

        Background Not Specified

• cellular phenotype
• abnormal apoptosis (MGI Ref ID J:90392)
  • 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

Psen1^tm1Shn/Psen1^tm1Shn

        involves: 129S7/SvEvBrd * C57BL/6

• lethality-prenatal/perinatal
• neonatal lethality (MGI Ref ID J:40365)
  • none survive for longer than 30 min after natural birth or C-section
• embryogenesis phenotype
• abnormal rostral-caudal axis patterning (MGI Ref ID J:40365)
  • shorter rostro-caudal body axes
• abnormal rostral-caudal patterning of the somites (MGI Ref ID J:40365)
  • the segmentation in the caudal region of the somites appears less distinct at E9.5-10.5
• cardiovascular system phenotype
• intracranial hemorrhage (MGI Ref ID J:40365)
  • intracranial hemorrhage with varying degrees of severity and time of onset that can appear as early as E12.5
• craniofacial phenotype
• abnormal occipital bone morphology (MGI Ref ID J:40365)
  • occipital bones are underdeveloped
• growth/size phenotype
• abnormal postnatal growth/weight/body size (MGI Ref ID J:40365)
  • thick neck
• decreased body length (MGI Ref ID J:40365)
• decreased body weight (MGI Ref ID J:40365)
  • neonates weigh 15-20% less than control littermates
• limbs/digits/tail phenotype
• abnormal hindlimb morphology (MGI Ref ID J:40365)
  • hindlimbs are curved toward the midline
• curly tail (MGI Ref ID J:40365)
  • tails are curled toward the right side of the body
• kinked tail (MGI Ref ID J:40365)
  • by E12.5, all mutants display a kinked tail
• short tail (MGI Ref ID J:40365)
• nervous system phenotype
• abnormal brain morphology (MGI Ref ID J:40365)
  • 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 (MGI Ref ID J:40365)
  • cortical plate is thinner
  • 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 diencephalon morphology (MGI Ref ID J:40365)
  • the ependymal layer and the ventricular zone at the diencephalic sulcus are disrupted
• abnormal third ventricle morphology (MGI Ref ID J:40365)
  • the ventricular zone along the mid-portions of the third ventricle is absent in E14.5 mutants
• abnormal temporal lobe morphology (MGI Ref ID J:40365)
  • atrophy in the subcortical region of the temporal lobe along the external capsule in the brain
• abnormal dentate gyrus morphology (MGI Ref ID J:40365)
  • dentate gyrus is less distinct than in controls at E17.5
• abnormal hippocampus development (MGI Ref ID J:40365)
  • hippocampal formation is hardly recognizable at E14.5, whereas in controls it is quite prominent
• dilated lateral ventricles (MGI Ref ID J:40365)
• small telencephalic vesicles (MGI Ref ID J:40365)
  • smaller at E9.5
• abnormal lateral ganglionic eminence morphology (MGI Ref ID J:40365)
  • the lateral ganglionic eminence is much less prominent starting at E12.5 than in controls
  • fewer dividing progenitor cells in the luminal layer of the ventricular zone in the lateral ganglionic eminence, resulting in a thinner ventricular zone
• abnormal neurogenesis (MGI Ref ID J:40365)
• decreased neuronal precursor cell number (MGI Ref ID J:40365)
  • the ventricular and subventricular zones in the ventrolateral region show severe loss of neural progenitor cells leading to symmetric cavitation at E17.5
• intracranial hemorrhage (MGI Ref ID J:40365)
  • intracranial hemorrhage with varying degrees of severity and time of onset that can appear as early as E12.5
• neuron degeneration (MGI Ref ID J:40365)
  • 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
  • exhibit a progression of neuronal loss from anterior to posterior portions of the cerebral hemispheres
• respiratory system phenotype
• abnormal respiratory alveoli morphology (MGI Ref ID J:40365)
  • the alveoli are poorly expanded, probably due to mechanical difficulties imposed by the malformed ribcage
• skeleton phenotype
• abnormal axial skeleton morphology (MGI Ref ID J:40365)
  • axial skeleton is severely malformed
  • caudal to the pelvis, the axial skeletal structure is completely missing
• abnormal occipital bone morphology (MGI Ref ID J:40365)
  • occipital bones are underdeveloped
• abnormal rib morphology (MGI Ref ID J:40365)
  • the posterior rib segments are missing and the existing ribs are underossified and fused
• abnormal rib-vertebral column attachment (MGI Ref ID J:40365)
  • 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
• decreased rib number (MGI Ref ID J:40365)
  • homozygotes have only 9-11 instead of 13 pairs of ribs
• rib fusion (MGI Ref ID J:40365)
  • existing ribs are fused
• abnormal spine curvature (MGI Ref ID J:40365)
  • lack the normal cervical and lumbar flexures of the vertebral column
• abnormal sternum morphology (MGI Ref ID J:40365)
  • sternum is shorter, thicker and lacks intersternebral cartilage
• short sternum (MGI Ref ID J:40365)
• vertebral fusion (MGI Ref ID J:40365)
• cervical vertebral fusion (MGI Ref ID J:40365)
• lumbar vertebral fusion (MGI Ref ID J:40365)
• sacral vertebral fusion (MGI Ref ID J:40365)
• abnormal osteogenesis (MGI Ref ID J:40365)
  • 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
• skin/coat/nails phenotype
• loose skin (MGI Ref ID J:40365)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Psen1tm1Shn
Allele Name		targeted mutation 1, Jie Shen
Allele Type		Targeted (knock-out)
Common Name(s)		PS1-;
Mutation Made By		Jie Shen,   Harvard Med Sch/ Brigham Women's Hosp
Strain of Origin		129S7/SvEvBrd-Hprt1
ES Cell Line Name		AB2.1
ES Cell Line Strain		129S7/SvEvBrd-Hprt1
Gene Symbol and Name		Psen1, presenilin 1
Chromosome		12
Gene Common Name(s)		AD3; Ad3h; FAD; PS-1; PS1; S182; alzheimer disease 3 homolog; presenilin-1;
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. [MGI Ref ID J:40365]

Genotyping

Genotyping Information

Genotyping Protocols

Psen1^tm1Shn, STD PCR, vers. 1

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

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):629-39. [PubMed: 9160754]  [MGI Ref ID J:40365]

Additional References

Psen1^tm1Shn related

Cook DG; Li X; Cherry SD; Cantrell AR. 2005. Presenilin 1 deficiency alters the activity of voltage-gated Ca2+ channels in cultured cortical neurons. J Neurophysiol 94(6):4421-9. [PubMed: 16148264]  [MGI Ref ID J:116810]

De Gasperi R; Gama Sosa MA; Wen PH; Li J; Perez GM; Curran T; Elder GA. 2008. Cortical development in the presenilin-1 null mutant mouse fails after splitting of the preplate and is not due to a failure of reelin-dependent signaling. Dev Dyn 237(9):2405-14. [PubMed: 18729224]  [MGI Ref ID J:138800]

Handler M; Yang X; Shen J. 2000. Presenilin-1 regulates neuronal differentiation during neurogenesis. Development 127(12):2593-606. [PubMed: 10821758]  [MGI Ref ID J:62163]

Mastrangelo P; Mathews PM; Chishti MA; Schmidt SD; Gu Y; Yang J; Mazzella MJ; Coomaraswamy J; Horne P; Strome B; Pelly H; Levesque G; Ebeling C; Jiang Y; Nixon RA; Rozmahel R; Fraser PE; St George-Hyslop P; Carlson GA; Westaway D. 2005. Dissociated phenotypes in presenilin transgenic mice define functionally distinct gamma-secretases. Proc Natl Acad Sci U S A 102(25):8972-7. [PubMed: 15951428]  [MGI Ref ID J:99874]

Mizuguchi R; Kriks S; Cordes R; Gossler A; Ma Q; Goulding M. 2006. Ascl1 and Gsh1/2 control inhibitory and excitatory cell fate in spinal sensory interneurons. Nat Neurosci 9(6):770-8. [PubMed: 16715081]  [MGI Ref ID J:110261]

Wen PH; De Gasperi R; Gama Sosa MA; Elder GA. 2004. Neural progenitor cells do not differentiate prematurely in presenilin-1 null mutant mice. Neurosci Lett 371(2-3):249-54. [PubMed: 15519767]  [MGI Ref ID J:94236]

Wen PH; De Gasperi R; Sosa MA; Rocher AB; Friedrich VL Jr; Hof PR; Elder GA. 2005. Selective expression of presenilin 1 in neural progenitor cells rescues the cerebral hemorrhages and cortical lamination defects in presenilin 1-null mutant mice. Development 132(17):3873-83. [PubMed: 16079160]  [MGI Ref ID J:100132]

Yang X; Klein R; Tian X; Cheng HT; Kopan R; Shen J. 2004. Notch activation induces apoptosis in neural progenitor cells through a p53-dependent pathway. Dev Biol 269(1):81-94. [PubMed: 15081359]  [MGI Ref ID J:90392]

Yang Y; Cook DG. 2004. Presenilin-1 deficiency impairs glutamate-evoked intracellular calcium responses in neurons. Neuroscience 124(3):501-5. [PubMed: 14980721]  [MGI Ref ID J:89996]

Yang Y; Kinney GA; Spain WJ; Breitner JC; Cook DG. 2004. Presenilin-1 and intracellular calcium stores regulate neuronal glutamate uptake. J Neurochem 88(6):1361-72. [PubMed: 15009636]  [MGI Ref ID J:107993]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. At least two animals carrying the mutation of interest will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location). This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

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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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