B6N(129S4)-A1cf^{tm1c(EUCOMM)Hmgu}/Rkor

Stock number: 031869
Product name: A1cf^fl
Research areas: Research Tools

Description

A1cf^FL mice have exon 4 of the APOBEC1 complementation factor (A1cf) gene, floxed, making these mice useful for studying RNA binding proteins and metabolic regulation.

Detailed description

The floxed A1cf strain was generated using embryonic stem cells provided by the International Knockout Mouse Consortium (KOMP). A1cf (APOBEC1 complementation factor) encodes a hormone sensitive RNA binding protein that is involved in the regulation fructose and glycerol metabolism in the liver. Exon 4 of the A1cf gene is flanked by loxP sites in this conditional mutant strain. Heterozygous and homozygous mice are healthy, appear normal, and are fertile. Global deletion of A1cf results in embryonic lethality.

When bred to mice expressing Cre recombinase in the liver (B6N.Cg-Speer6-ps1^{Tg(Alb-cre)21Mgn}/J, Stock 018961), resulting mice exhibit improved improved glucose tolerance as well as decreased susceptibility to fructose-induced hyperglycemia and obesity.

Development

The L1L2_Bact_P cassette was inserted at a position 31910623 of Chromosome 19 upstream of exon 4 of the APOBEC1 complementation factor (A1cf) gene. The cassette is composed of an FRT site followed by lacZ sequence and a loxP site. This first loxP site is followed by neomycin under the control of the human beta-actin promoter, SV40 polyA, a second FRT site and a second loxP site. A third loxP site was inserted downstream of exon 4. The construct was electroporated into C57BL/6N-A^tm1Brd derived JM8A3.N1 embryonic stem (ES) cells. Targeted ES cells were injected into blastocysts. The mice were bred to B6N.129S4-Gt(ROSA)26Sor^tm1(FLP1)Dym/J to excise the FRT-flanked lacZ and neo cassette leaving exon 4 flanked by loxP sites. Resulting A1cf^FL offspring were bred to C57BL/6NJ mice to remove the flp-expressing transgene, and were maintained on a C57BL/6NJ background for 6 generations. Sperm from this strain was cryopreserved in 2020.

Allele

Symbol: A1cf^{tm1c(EUCOMM)Hmgu}
Name: targeted mutation 1c, Helmholtz Zentrum Muenchen GmbH
MGI accession ID: MGI:6384908
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: A1cf
Marker name: APOBEC1 complementation factor
Marker synonyms: 1810073H04Rik; A1cft; ACF; ACF64; ACF65; Apobec-1; apobec-1 complementation factor; APOBEC1CF; ASP
Chromosome: 19
Strain of origin: C57BL/6N-A^tm1Brd
Molecular note: The L1L2_Bact_P cassette was inserted at position 31888023 of Chromosome 19 upstream of the critical exon 4 (Build GRCm39). The cassette is composed of an FRT site followed by lacZ sequence and a loxP site. This first loxP site is followed by a neomycin resistance gene under the control of the human beta-actin promoter, SV40 polyA, a second FRT site and a second loxP site. A third loxP site is inserted downstream of the targeted exon 4 at position 31888936. The critical exon 4 is thus flanked by loxP sites. A "conditional ready" (floxed) allele was created by flp recombinase expression in mice carrying this allele. Subsequent cre expression results in a knockout mouse. Further information on targeting strategies used for this and other IKMC alleles can be found at http://www.informatics.jax.org/mgihome/nomen/IKMC_schematics.shtml