The ubiquitous CrT knockout allele (CrT-) has a deletion of the exons encoding the 2nd-4th transmembrane domain of the creatine transporter gene on the X chromosome. These mice may be useful for studying creatine transport and human X-linked creatine deficiency syndrome, mental retardation, autism, and speech, language, cognitive, and memory disorders.
Joseph F Clark, University of Cincinnati
|Allele Type||Gene Symbol||Gene Name|
|Targeted||Slc6a8||solute carrier family 6 (neurotransmitter transporter, creatine), member 8|
The ubiquitous CrT knockout allele (CrT-) has a deletion of the exons encoding the 2nd-4th transmembrane domain of the creatine transporter gene on the X chromosome. Heterozygous females (CrT+/-) are viable and fertile with no observed abnormalities. Hemizygous males (CrT-/Y) do not breed (perhaps due to behavioral/cognitive phenotype; fertility is unknown). No homozygous females have been generated to date (January 2013). Males hemizygous for the pan deletion (CrT-/Y) lack creatine in brain and muscle, have significant creatine reductions in other tissues (including heart and testis), and exhibit learning and memory deficits resembling human X-linked creatine deficiency syndrome.
Of note, the donating investigator also sent the CrTflox conditional mice (floxed exons 2-4) to The Jackson Laboratory Repository as Stock No. 020642.
A targeting vector was designed by Dr. Joseph F. Clark (University of Cincinnati) to insert a loxP site upstream of exon 2, and an frt-flanked neo cassette and second loxP site downstream of exon 4 of the creatine transporter gene (CrT; Slc6a8) on the X chromosome. The construct was electroporated into C57BL/6-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient MF-1 blastocysts. Chimeric males were bred with C57BL/6J females to generate the conditional founder mice. To remove the frt-flanked neo cassette, mice were bred with the germline FLP deleter strain (B6;SJL-Tg(ACTFLPe)9205Dym/J; Stock No. 003800). Offspring with the CrTflox allele (loxP site upstream of exon 1, and a single frt site and second loxP site downstream of exon 4) were obtained. The CrTflox mice were bred to C57BL/6J wildtype mice for several generations (and the FLP transgene was removed) prior to sending to The Jackson Laboratory Repository in 2013 as Stock No. 020642. Upon arrival, some CrTflox mice were bred to animals expressing Cre recombinase in the germline (B6.Sox2Cre; Stock No. 008454) to remove floxed exons 2-4. Offspring with the ubiquitous CrT knockout allele (CrT-) were established. Heterozygous females were bred to C57BL/6J wildtype males to remove the Sox2Cre transgene. The CrT- colony was then maintained by breeding heterozygous females with wildtype males from the colony or with C57BL/6J inbred males.
|Allele Name||targeted mutation 1.2, Joseph Clark|
|Gene Symbol and Name||Slc6a8, solute carrier family 6 (neurotransmitter transporter, creatine), member 8|
|Gene Synonym(s)||AA589632; CCDS1; CHOT1; CHT1; CRT; CRTR; CT1; CTR5; Creat; Creat; creatine transporter; expressed sequence AA589632|
|Strain of Origin||C57BL/6|
|Molecular Note||Cre-mediated recombination of Slc6a8tm1.1Clar removed exons 2, 3, and 4.|
The targeted mutation is on the X chromosome. Heterozygous females have no reported breeding problems. Hemizygous males do not breed (perhaps due to behavioral/cognitive phenotype; fertility is unknown). When maintaining a live colony, heterozygous females are bred with wildtype males from the colony or with C57BL/6J inbred males (Stock No. 000664).
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