These Fmr1 knockout mice may be useful in applications related to the study of Fragile X Syndrome.
Dr. Stephen T. Warren, Emory University School of Medicine
Ben A Oostra, Erasmus University
These Fmr1 knockout mice have a neomycin resistance cassette replacing exon 5 of the fragile X mental retardation syndrome 1 (Fmr1) gene. Defects in FMR1 cause Fragile X syndrome, one of the most common forms of inherited mental retardation. Fragile X syndrome is associated with an array of deficits in motor control, cognition, learning, and memory, although their overall brain morphology is generally normal. Male hemizygotes and female homozygotes are viable and fertile. Male hemizygotes show macroorchidism (enlarged testes). Macroorchidism in caused by an increased rate of Sertoli cell proliferation during embryogenesis which may be independent of FSH signalling. Male hemizygotes and females homozygotes also exhibit hyperactivity, learning deficits, altered dendritic spines of visual cortex pyramidal cells, and differences in a variety of behavioral tests. Comparison of homozygotes to wildtype littermates in hidden- and visible-platform water maze learning showed deficits in spatial learning and motor performance.
The targeted mutation was made in the laboratory of Dr. Ben Oostra at Erasmus University in the Netherlands by replacing exon 5 of the fragile X mental retardation syndrome 1 (Fmr1) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected to C57BL/6J blastocysts and resulting males were bred to C57BL/6J females. These mice were backcrossed to C57BL/6J mice (Stock No. 000664) for five generations. Upon arrival at The Jackson Laboratory, these mice were bred to C57BL/6J mice.
As of July 2020, the live colony has been backcrossed to C57BL/6J mice a total equivalent of nine generations [N5F9pN4F1].
|Allele Name||targeted mutation 1, Ben Oostra|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Fmr1 KO; Fmr1tm4Cgr; FMRP KO; fmr-tm1Cgr; FraX|
|Gene Symbol and Name||Fmr1, fragile X mental retardation 1|
|Strain of Origin||129P2/OlaHsd|
|General Note||Genbank: AF179463 and AF170530|
|Molecular Note||A neomycin resistance gene was inserted into exon 5. RT-PCR analysis on testis RNA derived from hemizygous male mice demonstrated that no detectable transcript was produced from this allele, and western blot analysis on extracts of testes, liver, kidney and brain of hemizygous male mice confirmed that no stable encoded protein was made.|
|Mutations Made By|| |
Ben Oostra, Erasmus University
When maintaining a live colony, homozygous females can be bred with hemizygous males. Fmr1 is an X linked gene. Expected coat color from breeding:Black
When using the B6.129P2-Fmr1tm1Cgr/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #003025 in your Materials and Methods section.