Strain Name:

B6.129S4-Adcyap1tm1Clw/J

Stock Number:

009641

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Cryopreserved - Ready for recovery

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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.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator James Waschek,   UCLA

Description
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.

Development
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.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Adcyap1tm1Clw/Adcyap1tm1Clw

        B6.129S4-Adcyap1tm1Clw
  • nervous system phenotype
  • abnormal microglial cell activation
    • saline-treated mice exhibit an increase in number of large diameter microglia (activated) and a decrease in number of small diameter microglia (resting) as compared to saline-treated wild type; no significant changes are observed between paraquat-treated mutant and control mice   (MGI Ref ID J:194151)
  • decreased dopaminergic neuron number
    • mutant mice exhibit a 30% reduction of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra following a single dose (10 mg/kg) of the insecticide paraquat, although total number of neurons is not reduced   (MGI Ref ID J:194151)
  • increased susceptibility to dopaminergic neuron neurotoxicity   (MGI Ref ID J:194151)
  • immune system phenotype
  • abnormal T cell activation
    • induction of regulatory T cells is impaired in lymph nodes following administration of paraquat   (MGI Ref ID J:194151)
  • abnormal microglial cell activation
    • saline-treated mice exhibit an increase in number of large diameter microglia (activated) and a decrease in number of small diameter microglia (resting) as compared to saline-treated wild type; no significant changes are observed between paraquat-treated mutant and control mice   (MGI Ref ID J:194151)
  • abnormal regulatory T cell physiology
    • induction of regulatory T cells is impaired in lymph nodes following administration of paraquat   (MGI Ref ID J:194151)
  • increased T-helper 17 cell number
    • a single dose (10 mg/kg) of the insecticide paraquat increased numbers of Th17 cells in both spleen and blood, but not in lymph nodes   (MGI Ref ID J:194151)
  • homeostasis/metabolism phenotype
  • increased susceptibility to dopaminergic neuron neurotoxicity   (MGI Ref ID J:194151)
  • hematopoietic system phenotype
  • abnormal T cell activation
    • induction of regulatory T cells is impaired in lymph nodes following administration of paraquat   (MGI Ref ID J:194151)
  • abnormal microglial cell activation
    • saline-treated mice exhibit an increase in number of large diameter microglia (activated) and a decrease in number of small diameter microglia (resting) as compared to saline-treated wild type; no significant changes are observed between paraquat-treated mutant and control mice   (MGI Ref ID J:194151)
  • abnormal regulatory T cell physiology
    • induction of regulatory T cells is impaired in lymph nodes following administration of paraquat   (MGI Ref ID J:194151)
  • increased T-helper 17 cell number
    • a single dose (10 mg/kg) of the insecticide paraquat increased numbers of Th17 cells in both spleen and blood, but not in lymph nodes   (MGI Ref ID J:194151)
  • cellular phenotype
  • increased susceptibility to dopaminergic neuron neurotoxicity   (MGI Ref ID J:194151)

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Adcyap1tm1Clw/Adcyap1tm1Clw

        involves: 129S4/SvJae * C57BL/6
  • mortality/aging
  • partial preweaning lethality
    • 50-80% of the expected number of homozygotes are found at the time of genotyping   (MGI Ref ID J:94880)
  • behavior/neurological phenotype
  • abnormal circadian phase
    • a significant shortening of the phase angle of entrainment is seen   (MGI Ref ID J:94880)
    • in constant dark, a significant reduction in the phase advance induced by a single discrete light treatment is seen when either bright or dim light is used   (MGI Ref ID J:94880)
  • hyperactivity
    • increased wheel-running activity is seen with a 12:12 light:dark cycle   (MGI Ref ID J:94880)
  • shortened circadian period
    • the free running period is about 20 minutes shorter, however no difference in synchronization to a light dark cycle or responding to shifts in the light dark cycle are seen   (MGI Ref ID J:94880)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Immunology, Inflammation and Autoimmunity Research
Autoimmunity
      experimental allergic encephalomyelitis (EAE)

Metabolism Research
Free Radical Research

Neurobiology Research
Behavioral and Learning Defects
Circadian Rhythms

Reproductive Biology Research
Fertility Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Adcyap1tm1Clw
Allele Name targeted mutation 1, Christopher S Colwell
Allele Type Targeted (knock-out)
Common Name(s) PACAP-;
Mutation Made By James Waschek,   UCLA
Strain of Origin129S4/SvJae
Gene Symbol and Name Adcyap1, adenylate cyclase activating polypeptide 1
Chromosome 17
Gene Common Name(s) PACAP;
Molecular Note Exons 3, 4 and part of 5 were replaced with a neomycine resistance cassette. RIA analysis confirmed the absence of protein product. [MGI Ref ID J:94880]

Genotyping

Genotyping Information

Genotyping Protocols

Adcyap1tm1Clw, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Colwell CS; Michel S; Itri J; Rodriguez W; Tam J; Lelievre V; Hu Z; Waschek JA. 2004. Selective deficits in the circadian light response in mice lacking PACAP. Am J Physiol Regul Integr Comp Physiol 287(5):R1194-201. [PubMed: 15217792]  [MGI Ref ID J:94880]

Additional References

Adcyap1tm1Clw related

Armstrong BD; Abad C; Chhith S; Cheung-Lau G; Hajji OE; Nobuta H; Waschek JA. 2008. Impaired nerve regeneration and enhanced neuroinflammatory response in mice lacking pituitary adenylyl cyclase activating peptide. Neuroscience 151(1):63-73. [PubMed: 18055122]  [MGI Ref ID J:130746]

Dragich JM; Loh DH; Wang LM; Vosko AM; Kudo T; Nakamura TJ; Odom IH; Tateyama S; Hagopian A; Waschek JA; Colwell CS. 2010. The role of the neuropeptides PACAP and VIP in the photic regulation of gene expression in the suprachiasmatic nucleus. Eur J Neurosci 31(5):864-75. [PubMed: 20180841]  [MGI Ref ID J:159524]

Girard BA; Lelievre V; Braas KM; Razinia T; Vizzard MA; Ioffe Y; El Meskini R; Ronnett GV; Waschek JA; May V. 2006. Noncompensation in peptide/receptor gene expression and distinct behavioral phenotypes in VIP- and PACAP-deficient mice. J Neurochem 99(2):499-513. [PubMed: 17029602]  [MGI Ref ID J:119672]

Hatanaka M; Tanida M; Shintani N; Isojima Y; Kawaguchi C; Hashimoto H; Kakuda M; Haba R; Nagai K; Baba A. 2008. Lack of light-induced elevation of renal sympathetic nerve activity and plasma corticosterone levels in PACAP-deficient mice. Neurosci Lett 444(2):153-6. [PubMed: 18722505]  [MGI Ref ID J:141019]

Hirose M; Niewiadomski P; Tse G; Chi GC; Dong H; Lee A; Carpenter EM; Waschek JA. 2011. Pituitary adenylyl cyclase-activating peptide counteracts hedgehog-dependent motor neuron production in mouse embryonic stem cell cultures. J Neurosci Res 89(9):1363-74. [PubMed: 21674568]  [MGI Ref ID J:175565]

Lacombe A; Lelievre V; Roselli CE; Salameh W; Lue YH; Lawson G; Muller JM; Waschek JA; Vilain E. 2006. Delayed testicular aging in pituitary adenylate cyclase-activating peptide (PACAP) null mice. Proc Natl Acad Sci U S A 103(10):3793-8. [PubMed: 16505386]  [MGI Ref ID J:107140]

Tan YV; Abad C; Lopez R; Dong H; Liu S; Lee A; Gomariz RP; Leceta J; Waschek JA. 2009. Pituitary adenylyl cyclase-activating polypeptide is an intrinsic regulator of Treg abundance and protects against experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 106(6):2012-7. [PubMed: 19190179]  [MGI Ref ID J:144951]

Tan YV; Abad C; Wang Y; Lopez R; Waschek JA. 2013. Pituitary adenylate cyclase activating peptide deficient mice exhibit impaired thymic and extrathymic regulatory T cell proliferation during EAE. PLoS One 8(4):e61200. [PubMed: 23613811]  [MGI Ref ID J:200113]

Watson MB; Nobuta H; Abad C; Lee SK; Bala N; Zhu C; Richter F; Chesselet MF; Waschek JA. 2013. PACAP deficiency sensitizes nigrostriatal dopaminergic neurons to paraquat-induced damage and modulates central and peripheral inflammatory activation in mice. Neuroscience :. [PubMed: 23500093]  [MGI Ref ID J:194151]

Yan Y; Zhou X; Pan Z; Ma J; Waschek JA; DiCicco-Bloom E. 2013. Pro- and anti-mitogenic actions of pituitary adenylate cyclase-activating polypeptide in developing cerebral cortex: potential mediation by developmental switch of PAC1 receptor mRNA isoforms. J Neurosci 33(9):3865-78. [PubMed: 23447598]  [MGI Ref ID J:196063]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhen 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.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2085.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2710.50
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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.
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