α-Gal A- mice contain a neo cassette replacing exon 3 and intron 3 of the galactosidase, alpha (Gla) gene, abolishing gene expression. These mice may be useful when studying the pathogenesis of Fabry disease.
Ashok B Kulkarni, NIDCR NIH
α-Gal A- mice contain a neo cassette replacing exon 3 and intron 3 of the galactosidase, alpha (Gla) gene, abolishing gene expression. GLA is an X-linked gene that encodes a neuroendocrine peptide that is expressed in the central and peripheral nervous systems and also the gastrointestinal tract, pancreas, adrenal gland and urogenital tract. Mutations in GLA have been associated with the development of Fabry disease, a lysosomal storage disorder caused by a buildup of a fat called globotriaosylceramide. Fabry disease is characterized by pain, particularly in the hands and feet (acroparesthesias), angiokeratomas, hypohidrosis, corneal opacity, gastrointestinal issues, tinnitus, and hearing loss. Fabry disease can also lead to life-threatening complications such as progressive kidney damage, heart attack, and stroke. Mutations have also been associated with Alzheimer's disease, epilepsy, depression, eating disorders, and impaired cognitive function.
Hemizyogous males display abnormal kidney and liver morphology, both with accumulations of globotriaosylceramide. They also exhibit mild cardiomyopathy and abnormal cardiovascular physiology.
Of note, this allele is also available on a C57BL/6J-congenic background (Stock No. 036174).
The α-Gal A- targeting vector was designed to replace exon 3 and intron 3 of the galactosidase, alpha (Gla) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6 females. These mice were maintained on a mixed genetic background prior to sending males to The Jackson Laboratory Repository. Upon arrival, sperm was cryopreserved. To generate our live colony, an aliquot of the frozen sperm was used to fertilize oocytes from B6129SF1/J mice (Stock No. 101043).
|Allele Name||targeted mutation 1, Ashok B Kulkarni|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||alpha-Gal A -/0; alpha-galA-; Gla-|
|Gene Symbol and Name||Gla, galactosidase, alpha|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A 1kb genomic fragment containing part of exon 3 and intron 3 was replaced by a neomycin resistance cassette.|
|Mutations Made By|| |
Ashok Kulkarni, NIDCR NIH
Gal is an X-linked gene. When maintaining a live colony, homozygous females may be bred to hemizygous males.
When using the α-Gal A KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #003535 in your Materials and Methods section.