Mice homozygous for the Fmr1tm1Cgr targeted mutation show macroorchidism (enlarged testes), learning deficits, and hyperactivity. Macroorchidism in caused by an increased rate of Sertoli cell proliferation during embryogenesis which may be independent of FSH signalling. Comparison of homozygotes to wildtype littermates in hidden- and visible-platform water maze learning showed deficits in spatial learning and motor performance.
The Fmr1tm1Cgr targeted mutation was made in the laboratory of Dr. Ben Oostra at Erasmus University in the Netherlands. Exon 5 was disrupted by the positive selection marker gene neomycin. The negative selection marker gene thymidine kinase (tk) was inserted 3' of the genomic sequence in the polylinker of the vector. 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 to confirm germline transmission. The donating investigator reported that this line is on a mixed FVB and 129 background.
|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.
When using the FMR1- mouse strain in a publication, please cite the originating article(s) and include JAX stock #002700 in your Materials and Methods section.