The verified strain designations contain the APP Swedish mutation (APPswe) and the PSEN1 exon-9 deletion (PSEN1dE9).[S1][S2] The associated 2004 study reports that mutant presenilins specifically elevate the 42-residue amyloid-beta peptide in vivo.[S3] Those are molecular and animal-model observations. They do not establish the cause, course, or treatment response of Alzheimer disease in patients.
Questions the study can address
Study question
What to predefine
Amyloid-beta biology
Specify whether the primary endpoint is Aβ42, Aβ40, their ratio, or tissue deposition. The 2004 study specifically addresses elevation of Aβ42.[S3]
Background and age
State the exact strain designation, genetic background, age, and sex. Do not treat results from one colony or background as interchangeable with another.
Functional endpoints
Predefine the behavioral or physiological assay, its timing, and the analysis plan. A functional endpoint in mice is not a diagnosis of cognitive impairment in people.
Verified paper
Mutant presenilins and the 42-residue amyloid-beta peptide[S3]
The paper by Jankowsky and colleagues was published in Human Molecular Genetics in 2004, volume 13, issue 2, pages 159-170.[S3] Its title states the narrow finding relevant here: mutant presenilins specifically elevated the 42-residue amyloid-beta peptide in vivo.[S3] Use the paper to support that mechanistic claim, not a broader claim that the mouse predicts cognitive decline or treatment response in patients.
Use the journal DOI record for the paper rather than the secondary Mayo Clinic profile.[S3]
The Jackson Laboratory maintains the record for Stock No. 004462 and states that the strain is now hosted by the NIH Mutant Mouse Resource and Research Centers, which partners with JAX for distribution.[S1] Confirm the available material, lead time, background, and colony-generation plan before fixing a study date.
Item
Verified information or sponsor check
Record
JAX Stock No. 004462; hosted and distributed through the NIH MMRRC in partnership with JAX.[S1]
The MMRRC record identifies this strain as Stock No. 034829-JAX and says that cryopreserved material may be available on request.[S2] The original claim that plaques appear at about 6 to 7 months was not supported by the page-specific research and is not carried into the US version.
The MMRRC record says cryopreserved material may be available on request; confirm format and timing directly.[S2]
Current strain record: Mutant Mouse Resource and Research Center.[S2]
Commissioning checklist
Two related records were verified: JAX Stock No. 004462, now hosted through the NIH MMRRC, and MMRRC Stock No. 034829-JAX.[S1][S2] Do not order by the shorthand “APP/PS1” alone. Put the complete strain designation, source record, genetic background, age, sex, material format, and assay plan into the protocol.
Interpret the resulting data as measurements in a defined mouse strain. They can support a mechanistic or candidate-selection decision, but they do not establish efficacy, safety, or cognitive benefit in patients.
Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. https://doi.org/10.1093/hmg/ddh019 (accessed 2026-09-03)
3 Recommended Contract Research Organizations
for Non-Clinical Studies
— by Target goal and Expertise
In non-clinical development, the choice of contract research organization shapes the quality of the data and the time it takes to reach the next decision. Below, three CROs are introduced by the type of study they support: pharmacology (efficacy) studies, safety studies, and pharmacokinetic (PK/PD) studies. Each summary describes the services the company offers so that you can match a provider to your target and development objective.
Pharmacology (Efficacy) StudiesDisease-Relevant Models for Translational Drug Evaluation
Reference: SMC Laboratories, Inc. official website (https://www.smccro-lab.com/)
SMC Laboratories, Inc.
SMC Laboratories is a specialized non-clinical CRO focused on in vivo pharmacology and efficacy studies using disease-relevant animal models, particularly in fibrosis, inflammation, metabolic diseases, and oncology.
Areas of Expertise
Disease-Relevant Model Portfolio
SMC Laboratories offers models covering the liver, lung, kidney, intestine, and oncology. Its portfolio includes the proprietary STAM™ model for MASH, fibrosis, and hepatocellular carcinoma.
Study Design Based on Target Biology
Study plans are developed around the target biology, mechanism of action, disease stage, and development objective. Pharmacological endpoints can be combined with histopathology, biomarkers, and disease-specific readouts.
Support from Target Validation to Proof of Concept
With experience from more than 1,000 studies for clients in 30 countries, SMC Laboratories supports programs from target validation and candidate selection through in vivo proof-of-concept studies.
Safety StudiesComprehensive Safety Assessment for Preclinical Development
Reference: Charles River Laboratories official website (https://www.criver.com/)
Charles River Laboratories
Charles River provides non-clinical toxicology and safety assessment services for programs ranging from exploratory safety studies to IND-enabling development.
Areas of Expertise
General Toxicology Across Study Designs
Services include single- and repeat-dose toxicology, dose-range finding, and general toxicology studies across multiple species and administration routes.
Non-GLP and GLP Study Support
Charles River supports both non-GLP and GLP studies, allowing sponsors to progress from early safety characterization to studies intended for regulatory submissions.
Integrated IND-Enabling Safety Assessment
Toxicology studies can be integrated with toxicokinetics, clinical pathology, histopathology, and safety pharmacology to support interpretation and IND-enabling safety packages.
Pharmacokinetic (PK/PD) StudiesConnecting Drug Exposure with Pharmacological Response
Reference: Inotiv official website (https://www.inotiv.com/)
Inotiv
Inotiv provides integrated PK/PD, DMPK, and bioanalytical services to characterize drug exposure and its relationship with pharmacological response.
Areas of Expertise
Pharmacokinetic Characterization
PK studies characterize exposure, half-life, clearance, and other pharmacokinetic parameters needed to understand how a candidate behaves in the selected model.
Exposure–Response Evaluation
Pharmacokinetic data can be combined with pharmacodynamic endpoints and bioanalysis to evaluate the relationship between drug exposure and pharmacological response.
Integrated DMPK and Development Support
Integrated DMPK, pharmacology, and safety information supports candidate comparison, dose selection, dosing-frequency optimization, and decisions about subsequent preclinical development.
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