Sorl1*A528T SNP mice carry a CRISPR/Cas9-generated Sorl1 mutant allele containing an A528T point mutation. The Sorl1*A528T SNP mutation models a common, highly conserved missense variant (rs2298813) that is significantly associated with late-onset Alzheimer's disease and elevated Ab42 secretion.
Mike Sasner, The Jackson Laboratory
This Sorl1*A528T SNP strain carries a CRISPR/Cas9-generated A528T point mutation in exon 11 of the Sorl1 gene (sortilin-related receptor, LDLR class A repeats-containing).
The targeted Sorl1 gene encodes a mosaic protein and neuronal sorting receptor that is involved in endocytosis. Mutations of this gene have been associated with Alzheimer's disease. The Sorl1*A528T SNP mutation models models a common, highly conserved missense variant (rs2298813) that is significantly associated with late-onset AD.
Homozygous mice are viable and fertile. If additional characterization of these mice is performed, we may modify the strain description accordingly.
The Sorl1*A528T SNP allele was created by Dr. Michael Sasner (The Jackson Laboratory) using CRISPR/Cas9 endonuclease-mediated genome editing.
For the Sorl1em1Adiuj allele (Sorl1*A528T SNP): Plasmids encoding a single guide RNA designed to introduce the A528T point mutation (GCC->ACC; modeling human variant rs2298813), the silent R529R mutation into the sortilin-related receptor, LDLR class A repeats-containing gene (Sorl1), and the cas9 nuclease were introduced into the cytoplasm of B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J (Stock No. 028709)-derived fertilized eggs with well recognized pronuclei. Correctly targeted embryos were transferred to pseudopregnant females. Correctly targeted pups were identified by sequencing, and then bred to Stock No. 028709. The mice were then backcrossed to to C57BL/6J inbred mice (Stock No. 000664) and the Apoetm1.1(APOE*4)Adiuj and Trem2em1Adiuj alleles were removed.
|Allele Name||endonuclease-mediated mutation 1, MODEL-AD Center|
|Allele Type||Endonuclease-mediated (Humanized sequence)|
|Gene Symbol and Name||Sorl1, sortilin-related receptor, LDLR class A repeats-containing|
|Strain of Origin||B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J|
|Molecular Note||Plasmids encoding a single guide RNA designed to introduce the A528T point mutation (GCC to ACC; modeling human variant rs2298813) and silent R529R mutation into the gene and the cas9 nuclease were introduced into the cytoplasm of fertilized eggs with well recognized pronuclei.|
Both heterozygous and homozygous mice are viable and fertile.
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or to C57BL/6J inbred mice (Stock No. 000664).
Alternatively, homozygous mice may be bred together.
When using the Sorl1*A528T SNP mouse strain in a publication, please cite the originating article(s) and include JAX stock #032759 in your Materials and Methods section.
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.