STOCK Aldh1a3^tm1Gdu/J

Stock number: 018846
Research areas: Developmental Biology Research, Neurobiology Research, Research Tools

Description

In this Raldh3 KO strain exon 11 of the Aldh1a3, aldehyde dehydrogenase family 1, subfamily A3, gene is deleted. These mice exhibit abnormal eye development and a reduction of GABAergic neurons in the brain, and may have applications in studies of eye development, neurodevelopment, and retinoic acid signaling.

Detailed description

Aldehyde dehydrogenase isoform ALDH1A3 is responsible for the oxidation of retinaldehyde to retinoic acid in specific tissues and thus controls some aspects of retinoic acid signaling. These mice carry a targeted mutation of the Aldh1a3, aldehyde dehydrogenase family 1, subfamily A3, gene that has exon 11 deleted. Although homozygous embryos aged E14.5 undergo optic cup formation, the neural retina is thickened, the vitreous body is reduced, and a retrolenticular membrane develops between the retina and lens. Retinoic acid activity is reduced in homozygous embryos aged E10.5 to E14.5, with no activity detected in the ventral retina, olfactory pit, or forebrain basal ganglia, and reduced activity in the perioptic mesenchyme. Lateral ganglionic eminence (LGE) progenitor cells in the homozygous embryonic forebrain do not differentiate into GABAergic neurons resulting in a loss of GABAergic projection neurons in the striatum and a reduction of GABAergic interneurons in the olfactory bulb and cortex. Mice that are heterozygous for the targeted mutation are viable and fertile. Homozygotes die shortly after birth. No gene product (protein) is detected by immunohistochemical analysis of forebrain tissue from homozygous embryos aged E14.5.

Development

A targeting vector containing a PGK-NEO cassette and a loxP site was inserted downstream of exon 11. A second loxP site was inserted upstream of exon 11. The construct was electroporated into unspecified C57BL/6 derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to mice with germline expression of Cre recombinase (on the C57BL/6 background) to remove exon 11 and the PGK-NEO cassette. The mice were then crossed to Black Swiss outbred mice. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Aldh1a3^tm1Gdu
Name: targeted mutation 1, Gregg Duester
MGI accession ID: MGI:3512079
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Aldh1a3
Marker name: aldehyde dehydrogenase family 1, subfamily A3
Chromosome: 7
Strain of origin: C57BL/6
Molecular note: Exon 11 was removed via cre mediated recombination. Retinoic acid activity was absent from the ventral retina and olfactory pit at E10.5.