B6;129S1-Notch3^tm1Grid/2J

Stock number: 018910
Product name: Notch3^d1
Research areas: Cardiovascular Research, Developmental Biology Research, Research Tools

Description

These Notch3^d1 mutation is associated with abnormal arterial wall morphology. This mutant mouse strain may be useful in studies of the Notch pathway during development, vascular development and angiogenesis.

Of note, the Notch3^d1 allele is available with different amounts of C57BL/6J genome: Stock No. 010547 is three or more generations backcrossed onto C57BL/6J, whereas Stock No. 018910 is on a mixed C57BL/6J;129S1 genetic background.

Detailed description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected by Northern blot analysis of brain, lung and heart tissue or Western blot analysis of lung and brain tissue from homozygotes. Homozygotes exhibit disorganized artery wall morphology, and thin vascular smooth muscle cell coat and processes.

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. 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.

Development

A targeting vector containing a PGK-neo cassette was used to delete 2.5 kbp of sequence encoding the EGF repeats 8 through 12. The construct was electroporated into 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺ derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric males were bred to C57BL/6J females for germline transmission. The Notch3^d1 colony was then backcrossed to C57BL/6J inbred mice (Stock No. 000664) for three generations prior to sending to The Jackson Laboratory Repository in 2010 as Stock No. 010547. Upon arrival, mice were bred to C57BL/6J inbred mice to establish our live colony. In January 2014, the colony was bred once to B6129SF1/J mice (Stock No. 101043). Mice on a mixed C57BL/6;129S1 genetic background are Stock No. 018910.

Allele

Symbol: Notch3^tm1Grid
Name: targeted mutation 1, Tom Gridley
MGI accession ID: MGI:2687010
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Notch3^d1
Marker symbol: Notch3
Marker name: notch 3
Chromosome: 17
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Molecular note: A 2.5 kb genomic fragment containing sequence encoding EGF repeats 8 through 12 was replaced with a PGK-neo cassette inserted by homologous recombination. The absence of transcript and protein was indicated by Northern and Western blot analysis of homozygous mutant mice.