Mice that are homozygous for this targeted mutation of Adcyap1 (adenylate cyclase activating polypeptide 1) exhibit defective thermoregulation, hyperactivity, abnormal circadian phase shift, delayed testicular aging, increased sensitivity to experimental autoimmune encephalomyelitis (EAE) and impaired peripheral nerve axon regeneration. This mutant mouse strain may be useful in studies of photo-entrainment of circadian rhythm and other physiological changes induced by light, behavior, autoimmunity and inflammation, and peripheral nerve repair.
James Waschek, UCLA
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Adcyap1 | adenylate cyclase activating polypeptide 1 |
Mice that are homozygous for the targeted mutation are viable, but experience high postnatal mortality between postnatal week 1 and 2 due to thermoregulatory defect. The Donating Investigator reports that postnatal survival is improved if temperature is kept at 82.5 F. Homozygous males are fertile, homozygous females are subfertile. No gene product (protein) is detected by RIA (radioimmunoassay) analysis of hypothalamus, cerebral cortex, kidney, and stomach tissues in homozygotes. Homozygotes exhibit sustained hyperactivity, shortened circadian period and abnormal circadian phase shifting with 50% reduction in the magnitude of light cued phase shift. Homozygous mice lack the light stimulation increase of sympathetic nerve activity and plasma corticosterone that is observed in wildtype mice. Testicular aging is delayed in 15-month old male homozygotes; reactive oxygen species generation and apoptosis in the testis is reduced. Young male homozygotes (4 month old) exhibit decreased steroidogenesis with lower seminal vesicle weight, low testosterone level, and low expression levels of steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3βHSD). After crush injury, homozygotes have impaired peripheral nerve axon regeneration. Homozygotes also have increased sensitivity to experimental autoimmune encephalomyelitis (EAE). This mutant mouse strain may be useful in studies of photo-entrainment of circadian rhythm and other physiological changes induced by light, behavior, autoimmunity and inflammation, and peripheral nerve repair.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 3, 4 and part of exon 5a. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting male chimeric animals were crossed to C57BL/6 female mice, and then backcrossed to C57BL/6J (see SNP note below) for 11 generations.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 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. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.
Allele Name | targeted mutation 1, Christopher S Colwell |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | PACAP- |
Gene Symbol and Name | Adcyap1, adenylate cyclase activating polypeptide 1 |
Gene Synonym(s) | |
Strain of Origin | 129S4/SvJae |
Chromosome | 17 |
Molecular Note | Exons 3, 4 and part of 5 were replaced with a neomycin resistance cassette. RIA analysis confirmed the absence of protein product. |
Mutations Made By | James Waschek, UCLA |
When maintaining a live colony, these mice can be bred as heterozygotes. Homozygotes experience high postnatal mortality between postnatal week 1 and 2 due to thermoregulatory defect and homozygous females are subfertile. The Donating Investigator reports that postnatal survival is improved if temperature is kept at 82.5 F.
When using the B6.129S4-Adcyap1tm1Clw/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #009641 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous or Wild type for Adcyap1<tm1Clw> |
Frozen Mouse Embryo | B6.129S4-Adcyap1<tm1Clw>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129S4-Adcyap1<tm1Clw>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129S4-Adcyap1<tm1Clw>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.129S4-Adcyap1<tm1Clw>/J Frozen Embryo | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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