CBA.Cg-Chr 10^C57BL/6 Vip^tm1(cre)Zjh/AhsnJ

Stock number: 037964
Product name: Vip-IRES-cre
Research areas: Neurobiology Research, Research Tools

Description

Vip-IRES-Cre mice have Cre recombinase expression directed to Vip-expressing cells by the endogenous promoter/enhancer elements of the vasoactive intestinal polypeptide locus. Cre activity is detected in the neocortex, hippocampus, olfactory bulb, suprachiasmatic nuclei, and other discrete midbrain and brainstem regions. These mice may be useful to study neural GABAergic circuits throughout the mammalian brain.

While Vip-IRES-Cre was designed to retain endogenous Vip expression, a 2019 publication indicates this allele has reduced Vip expression - see details below. As such, researchers may use homozygous mice for routine colony maintenance, but should consider using heterozygous Vip-IRES-Cre mice and wildtype littermate controls in all their studies.

Of note, the same Vip-IRES-Cre knock-in allele is also available on a C57BL/6J genetic background as Stock No. 031628 and a STOCK background as Stock No. 010908.

Detailed description

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. The phenotype summarized below is for the parental line: Vip-IRES-Cre knock-in mice on a C57BL/6;129S4 genetic background (Stock No. 010908). It should be noted that the phenotype of this CBA/CaJ-congenic Vip-IRES-Cre knock-in line (Stock No. 037964) could vary from that of the parental line from which it was derived. The phenotype below describes the parental line (Stock No. 010908).

The Vip-IRES-Cre allele harbors an internal ribosome entry site and Cre recombinase in the 3' UTR of the vasoactive intestinal polypeptide locus (Vip). As such, it is designed to have the endogenous Vip promoter/enhancer elements directing cre expression in the neocortex, hippocampus, olfactory bulb, suprachiasmatic nuclei and other discrete midbrain and brainstem regions. When Vip-IRES-Cre mice are bred with mice containing loxP-flanked sequences, Cre-mediated recombination will result in deletion of the floxed sequences in the Vip-expressing cells in the offspring. While Vip-IRES-cre was designed to retain endogenous Vip expression, a 2019 publication indicates this allele has reduced Vip expression - see details below. As such, researchers may use homozygous mice for breeding, but should consider using heterozygous Vip-IRES-Cre mice and wildtype littermate controls in all their studies.

In 2010, the donating investigator for Stock No. 010908 reported Cre recombinase activity is specific and efficient (largely recapitulates the endogenous Vip expression pattern with highly efficient recombination). They report Cre recombinase activity in some GABAergic interneurons, and did not examine cre expression in the intestine or tissues other than brain. VIP expression from this Vip-IRES-Cre allele was not evaluated by the donating investigator (January 2010) - see additional details below. They also reported that homozygous mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities.

For characterization information, see images at the Allen Institute for Brain Science website (Vip-IRES-Cre images).

If the recombinase activity pattern of this allele is further characterized by the Genetic Resource Science group at The Jackson Laboratory, such findings will be reported on the Mouse Genome Informatics (MGI) Allele Detail entry (Vip^tm1(cre)Zjh). This same information would also be found searching the MGI Recombinase Activity database.

While this Vip-IRES-cre allele was designed as a 3' knock-in allele, Cheng et al. 2019 J Biol Rhythms (PMID:31452438) indicates the Vip-IRES-cre allele has reduced Vip expression. When examined at 2 days of age, Vip-IRES-cre heterozygotes exhibit reduced expression of the neuropeptide products encoded by the Vip gene (VIP and peptide histidine isoleucine [PHI]) in the suprachiasmatic nucleus (SCN) of the hypothalamic nucleus, when compared to wildtype littermates. The total number of VIP/PHI-positive neurons within the SCN was not different between Vip-IRES-cre heterozygotes and wildtype littermates - ruling out a potential loss of VIP/PHI neurons. Expression of other neuropeptides was not altered. The wheel-running activity rhythms of heterozygous mice were not affected.

Development

Mice harboring the Vip-IRES-Cre knock-in allele on a mixed genetic background were sent to The Jackson Laboratory Repository in 2010 (as Stock No. 010908).

Stock No. 010908 mice were obtained by Dr. Andrea Hasenstaub (University of California, San Francisco) who further backcrossed these mice to CBA/CaJ mice Stock No. 000654) for at least 6 generations to fix the C57BL/6-derived mutation associated with age related hearing loss on Chromosome 10 within the cadherin 23 (otocadherin) locus (Cdh23). Some of these mice were sent back to the The Jackson Laboratory as this new strain, Stock No. 037964. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize CBA/CaJ oocytes. Stock No. 037964 has agouti coat color.

In 2023, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Three of the 43 markers throughout the genome were segregating with C57BL/6, including markers on Chromosomes 12 and 17, as well as the Chromosome 10 Cdh23 locus.

Allele

Symbol: Vip^tm1(cre)Zjh
Name: targeted mutation 1, Z Josh Huang
MGI accession ID: MGI:4431361
Generation method: Targeted
Attributes: Recombinase-expressing
Synonyms: VIP-Cre; Vip-IRES-cre
Marker symbol: Vip
Marker name: vasoactive intestinal polypeptide
Marker synonyms: PHI, peptide histidine isoleucine; PHM27; vip/phi27
Chromosome: 10
Strain of origin: (C57BL/6 x 129S4/SvJae)F1
Expressed genes: cre,cre recombinase,bacteriophage P1
Site of expression: Cre recombinase activity is observed in some GABAergic interneurons.
Molecular note: A targeting vector was designed to insert an internal ribosome entry site (IRES), a cre recombinase sequence, an SV40 polyA signal, and an frt-flanked neo cassette into the 3' untranslated region (after the translational termination site) of the vasoactive intestinal polypeptide locus (Vip). This construct was electroporated into C57BL/6 x 129S4/SvJae hybrid embryonic stem (ES) cells. Chimeric mice were bred with Actin-FLPe mice (on a C57BL/6 congenic background) to generate the colony and remove the neo selection cassette. The FLPe transgene has been bred out of the line.