B6.129-Ncor1^tm1Rsd/J

Stock number: 028890
Product name: N-CoR ^-
Research areas: Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research

Description

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.

Detailed description

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.

Development

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

Symbol: Ncor1^tm1Rsd
Name: targeted mutation 1, Michael G Rosenfeld
MGI accession ID: MGI:2677822
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ncor1
Marker name: nuclear receptor co-repressor 1
Chromosome: 11
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.