The 5' SIN3 interaction domain (SID1) of Ncor1 is replaced with a neomycin resistance gene in this targeted knockout allele. Homozygous embryos die between E13.5 and E15.5 and exhibit defects in developmental progression of specific erythrocyte, thymocyte, and neural events.
Michael Geoff Rosenfeld, University of California, San Diego
Ncor1 (nuclear receptor co-repressor 1; N-CoR) is a regulator of erythrocyte, thymocyte and neural development processes.
A 3 kb genomic sequence encoding the 5' SIN3 interaction domain (SID1) in Ncor1 is replaced with a neomycin resistance gene in this targeted knockout allele. Protein expression is not detectable in mouse embryonic fibroblasts (MEFs) derived from homozygotes. Homozygous embryos die between E13.5 and E15.5 and exhibit defects in developmental progression of specific erythrocyte, thymocyte, and neural events. Homozygotes demonstrate a red blood cell development deficiency, T cell development deficiency, and a neuronal deficiency.
At E13.5, homozygous embryos are markedly pale, anemic, and on average 80% smaller than wildtype or heterozgyous littermates. Hematocrit levels are severely reduced. Peripheral blood smears from these mice show fewer non-nucleated erythroctyes, but many more nucleated erythroblasts than wildtype controls.
At E14.5, the thymus is markedly smaller in homozygous embryos. The total number of live thymocytes is reduced approximately 8-fold in cultured thymii, and an increased rate of cell death is observed. T cell development is arrested at the double-negative stage, with only 3% of thymocytes expressing both CD4 and CD8.
The relative size of the developing thalamus is reduced in homozygous embryos by E12.5, becoming increasingly more pronounced by E15. Nissl-staining of coronal brain sections reveals that specific thalamic nuclei, such as the lateral geniculate nucleus, are markedly smaller in homozygous embryos. No evidence of apoptosis is detected. Data suggests that this gene is a principal regulator of neural stem cells, and controls differentiation of neural stem cells into astrocytes.
A 3 kb genomic sequence including amino acids 282-308 in the 5' SIN3 interaction domain (SID1) was replaced with a PGK-neomycin cassette, inducing a frameshift via homologous recombination in (129X1/SvJ x 129S1/Sv)F1- Kitl+-derived R1 embryonic stem (ES) cells. Resultant chimeric mice were crossed primarily with C57BL/6NCrl mice (some crosses with C57BL/6J) for at least 10-15 generations.
|Allele Name||targeted mutation 1, Michael G Rosenfeld|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||N-CoR -|
|Gene Symbol and Name||Ncor1, nuclear receptor co-repressor 1|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||A neomycin selection cassette replaced a 3 kb genomic fragment containing the coding sequences for the Sin3 interaction domain. Western blot analysis on lysates derived from MEFs of homozygous mice demonstrated that no detectable protein was produced from this allele.|
Heterozygotes are viable and fertile. Homozygotes are embryonic lethal at E13.5-E15.5.
When using the N-CoR - mouse strain in a publication, please cite the originating article(s) and include JAX stock #028890 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.