nNos KO mice may useful when studying structure and function of neurons and their synaptic connections in the brain and periphery.
IMR Colony, The Jackson Laboratory
The mice of this strain have been backcrossed more than 10 backcrosses to C57BL/6J, making this strain more effective for studies of the Nos1 KO than the incipient stock (#002633).
The nitric oxide signaling molecule produced by the neuronal Nos1 gene is widely expressed, affecting diverse systems. The knockout of this gene has been shown to affect such normal functions as cognition and behavior, long-term memory, cortical development, colonic motility, skeletal muscle contractility, ovarian cycle regulation, cardiac/cardiovascular function, and certain immune system responses. Western blots of brain homogenates from homozygous mutant mice showed no detectable protein. However, splice variants are expressed and variable low levels of NOS activity are seen in the brain.
Heterozygous mice are viable and fertile, while some lethality is seen in homozygotes due to stomach hypertrophy. The first publication describing this knock-out reported that mutants have enlarged stomachs with hypertrophy of the pyloric sphincter and the circular muscle layer (Huang et al., 1993). Male homozygotes of this strain were initially reported to be more aggressive than control mice, but this has been since attributed to heterogeneity of the stock before it was sufficiently backcrossed to the C57BL/6J genetic background. The C57BL/6J-congenic strain at The Jackson Laboratory (Stock No. 002986) shows normal behavior in this regard.
The Jackson Laboratory preferred mating scheme for Stock No. 002986 is breeding heterozygous mice together, or by breeding heterozygous females to homozygous males. Breeding heterozygous mice together results in less than Mendelian ratios of homozygous pups. Of note, we attempted breeding homozygotes together and found they generated offspring at a much slower rate.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for this strain. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector was designed to replace exon 1 of the nitric oxide synthase 1, neuronal (Nos1) gene with a neomycin cassette. This exon encodes the initiation site and amino acids 1 - 159 of the protein. The targeting vector was electroporated into 129S4/SvJae
-derived Jl ES cells that were injected into C57BL/6 blastocysts. Injected blastocysts were implanted in (C57BL/6 x DBA/2)Fl mice. Chimeric progeny were backcrossed to C57BL/6 mice. Some mice were further backcrossed to C57BL/6J mice (Stock No. 000664) for more than 10 generations to produce this Stock No. 002986.
|Allele Name||targeted mutation 1, Paul L Huang|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||alphaNOS1; Kn; N2KO; nNOS-; nNOS KO; nNOS-; NOSdelta|
|Gene Symbol and Name||Nos1, nitric oxide synthase 1, neuronal|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A neomycin cassette replaced exon 1. This exon encodes the initiation site and amino acids 1 - 159 of the protein. Northern blots of brain homogenates from homozygous mutant mice showed no detectable mRNA. Western blots of brain homogenates from homozygous mutant mice showed no detectable protein. However, splice variants are expressed and variable low levels of NOS activity are seen in the brain.|
|Mutations Made By|| |
Dr. Paul Huang, Mass General Hospital, Harvard Med Sch
The Jackson Laboratory preferred mating scheme for Stock No. 002986 is breeding heterozygous mice together, or by breeding heterozygous females to homozygous males. Breeding heterozygous mice together results in less than Mendelian ratios of homozygous pups.
Of note, we attempted breeding homozygotes together and found they generated offspring at a much slower rate.
Some lethality related to stomach hypertrophy observed in homozygotes.
When using the nNOS KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #002986 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.