B6;129S4-Man1a2^tm1.1Ahe/J

Stock number: 007672
Research areas: Developmental Biology Research

Description

Mice that are homozygous for this targeted mutation have a perinatal lethal phenotype and die within hours of birth. At embryonic day 18.5 homozygous embryos exhibit reduced alveolar air space, thickened alveolar walls, small atelectactic areas and delayed lung development. This mutant mouse strain may be useful in studies of lung development and pulmonary physiology.

Detailed description

Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Homozygous mice have a perinatal lethal phenotype and die within hours of birth due to respiratory distress (cyanosis and alveolar hemorrhage). No gene product (mRNA) is detected by RT-PCR analysis of total RNA from homozygous embryonic tissues. At embryonic day 18.5 homozygous embryos exhibit reduced alveolar air space, thickened alveolar walls, small atelectactic areas and delayed lung development. This mutant mouse strain may be useful in studies of lung development and pulmonary physiology.

Development

A targeting vector, pflox, containing sequence encoding exon 2 and loxP site flanked neomycin resistance and herpes simplex virus thymidine kinase genes was utilized in the construction of this mutant. This construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a cre expression plasmid for the purpose of removing exon 2 and the selectable marker cassette. ES cells that had successfully undergone Cre recombination and no longer retained exon 2 or the selection cassette were were injected into C57BL/6 recipient blastocysts. Resulting chimeric animals were backcrossed to wildtype C57BL/6J mice.

Allele

Symbol: Man1a2^tm1.1Ahe
Name: targeted mutation 1.1, Annette Herscovics
MGI accession ID: MGI:3703789
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Man1a2
Marker name: mannosidase, alpha, class 1A, member 2
Chromosome: 3
Strain of origin: 129S4/SvJae
Molecular note: The floxed exon 2 in Man1a2^tm1Ahe was removed via transient transfection with Cre recombinase. Excision of the floxed exon causes a frameshift and introduces a stop codon immediately following exon 1. RT-PCR confirmed the loss of gene expression in various tissues.