B6.129-Mapk6^tm1Melo/J

Stock number: 027186
Product name: Erk3^-
Research areas: Developmental Biology Research, Internal/Organ Research, Neurobiology Research, Research Tools

Description

These Mapk6 (Erk3) lacZ knockin/knockout mice exhibit homozygous neonatal lethality characterized by delayed lung maturation, pulmonary hypoplasia, and intrauterine growth restriction. They may be useful for studygin fetal growth, lung maturation, neuromuscular phenotypes and immune function.

Detailed description

Mapk6 (Erk3) knockin/knockout mice contain a lacZ neomycin cassette in place of exons 2-4 of the mitogen-activated protein kinase 6 (Mapk6), abolishing gene function. Beta-galactosidase activity is detected in a range of developing tissues in E15.5 embryos. MAPK6 is a member of the mitogen-activated protein kinases also known as extracellular signal-regulated kinases (ERKs) that are activated in response to extracellular stimuli. Homozygous neonates die within 24 hours; 40% within 15 minutes due to acute respiratory failure. Pups exhibit delayed lung maturation, pulmonary hypoplasia, impaired saccular development, atelectasis, defective type II pulmonary differentiation, and neuromuscular defects. Intrauterine growth is restricted resulting in reduced fetal lung, heart and liver weights. Mapk6 deficiency also results in defective thymocyte development. This strain may be useful for studying fetal growth, lung maturation, neuromuscular phenotypes and immune function.

Development

A targeting vector containing a lacZ gene and neomycin resistance cassette fused in frame with the ATG initiation codon in exon 2 was used to disrupt exons 2, 3, and 4 resulting in total loss of transcription. Endogenous regulatory elements direct the transcription of the inserted neo/lacZ cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1–derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were bred to C57BL/6 mice and offspring were backcrossed to C57BL/6 for at least 6 generations. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Allele

Symbol: Mapk6^tm1Melo
Name: targeted mutation 1, Sylvain Meloche
MGI accession ID: MGI:4365549
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Mapk6
Marker name: mitogen-activated protein kinase 6
Chromosome: 9
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Expressed genes: lacZ,beta-galactosidase,E. coli
Site of expression: lacZ is detected in a range of developing tissues in E15.5 embryos.
Molecular note: Exons 2, 3, and 4 were replaced with a lacZ gene and neo cassette via homologous recombination. Quantitative RT-PCR and western blot analysis confirmed the absence of expression in lungs from homozygous mutants and homozygous MEFs, respectively.