Strain Name:

B6;129-Pcsk2tm1Dfs/J

Stock Number:

002963

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Availability:

Cryopreserved - Ready for recovery

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 Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating InvestigatorDr. Donald Steiner,   University of Chicago

Appearance
white-bellied agouti
Related Genotype: Aw/?

black
Related Genotype: a/a

Development
This strain was developed in the laboratory of Dr. Donald Steiner, HHMI Research Laboratories, The University of Chicago. Exon 3 of the Pcsk2 gene was interrupted using a vector containing the neo resistance gene. This results in a truncated transcript that is unstable, isn't secreted, and is unable to process protein precursors. The 129X1/SvJ x 129S1/Sv-derived R1 ES cell line was used for the targeted mutagenesis

Control Information

  Control
   Wild-type from the colony
   101045 B6129SF2/J (approximate)
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Pcsk2tm1Dfs/Pcsk2tm1Dfs

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6
  • cardiovascular system phenotype
  • increased systemic arterial blood pressure
    • significantly increased blood pressure when placed on a high salt diet (158mmHg)   (MGI Ref ID J:82967)
  • endocrine/exocrine gland phenotype
  • abnormal gland physiology
    • prohormone processing is incomplete   (MGI Ref ID J:41505)
    • abnormal pancreatic alpha cell physiology
      • alpha cell proliferation at E17.5 3X normal   (MGI Ref ID J:85590)
      • decreased glucagon secretion
        • no mature glucagons formed   (MGI Ref ID J:41505)
    • abnormal pancreatic somatostatin secretion
      • limited maturation of somatostatin   (MGI Ref ID J:41505)
    • decreased insulin secretion
      • limited formation of mature insulin   (MGI Ref ID J:41505)
  • abnormal pancreatic islet morphology   (MGI Ref ID J:41505)
    • abnormal pancreatic alpha cell morphology
      • increased volume of glucagon positive alpha cells   (MGI Ref ID J:41505)
    • abnormal pancreatic beta cell differentiation
      • beta cells first appear functionally at E15 (2 days late)   (MGI Ref ID J:85590)
    • decreased pancreatic beta cell number
      • modest reduction in beta cell numbers   (MGI Ref ID J:41505)
    • increased pancreatic delta cell number
      • increased number of somatostatin positive delta cells   (MGI Ref ID J:41505)
  • homeostasis/metabolism phenotype
  • decreased circulating glucose level
    • fasting blood sugar level was significantly reduced   (MGI Ref ID J:41505)
  • decreased circulating insulin level
    • low circulating insulin and elevated proinsulin   (MGI Ref ID J:41505)
  • decreased glucagon secretion
    • no mature glucagons formed   (MGI Ref ID J:41505)
  • decreased insulin secretion
    • limited formation of mature insulin   (MGI Ref ID J:41505)
  • decreased pituitary hormone level
    • reduced levels of gamma-MSH in the pituitary on both high and low salt diet   (MGI Ref ID J:82967)
  • impaired glucose tolerance
    • response to injected glucose was muted   (MGI Ref ID J:41505)
  • reproductive system phenotype
  • reduced female fertility
    • females produced fewer consecutive litters   (MGI Ref ID J:41505)
    • an increased number of pups were born dead   (MGI Ref ID J:41505)
  • cellular phenotype
  • abnormal pancreatic beta cell differentiation
    • beta cells first appear functionally at E15 (2 days late)   (MGI Ref ID J:85590)

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

Pcsk2tm1Dfs/Pcsk2tm1Dfs

        involves: 129S1/Sv * 129X1/SvJ * CD-1
  • behavior/neurological phenotype
  • analgesia
    • mutants exhibit increased opiate-mediated stress-induced analgesia compared to wild-type at both spinal (tail-flick test) and supraspinal (mechanical and hotplate tests) levels   (MGI Ref ID J:112641)
  • hyporesponsive to tactile stimuli
    • mutants show a higher latency in a mechanical nociception test (12 grams force vs baseline of 1.5 grams force to get response) 5 minutes following a warm swim   (MGI Ref ID J:112641)
  • increased thermal nociceptive threshold
    • mutants display higher latencies in tail-flick and hotplate tests 5 minutes following a warm swim (3 minutes at 33 degrees C)   (MGI Ref ID J:112641)
    • at 30 minutes after a warm swim, little difference compared to controls is seen   (MGI Ref ID J:112641)
    • mutants display higher latencies (1.5 fold x baseline) in hotplate tests 30 minutes following a cold swim (3 minutes at 10 degrees C) compared to controls (2-fold below baseline   (MGI Ref ID J:112641)
    • 5 minutes after a cold swim, both mutants and controls show similar increases above baseline for tail-flick and hot plate tests   (MGI Ref ID J:112641)
  • integument phenotype
  • analgesia
    • mutants exhibit increased opiate-mediated stress-induced analgesia compared to wild-type at both spinal (tail-flick test) and supraspinal (mechanical and hotplate tests) levels   (MGI Ref ID J:112641)
  • hyporesponsive to tactile stimuli
    • mutants show a higher latency in a mechanical nociception test (12 grams force vs baseline of 1.5 grams force to get response) 5 minutes following a warm swim   (MGI Ref ID J:112641)
  • increased thermal nociceptive threshold
    • mutants display higher latencies in tail-flick and hotplate tests 5 minutes following a warm swim (3 minutes at 33 degrees C)   (MGI Ref ID J:112641)
    • at 30 minutes after a warm swim, little difference compared to controls is seen   (MGI Ref ID J:112641)
    • mutants display higher latencies (1.5 fold x baseline) in hotplate tests 30 minutes following a cold swim (3 minutes at 10 degrees C) compared to controls (2-fold below baseline   (MGI Ref ID J:112641)
    • 5 minutes after a cold swim, both mutants and controls show similar increases above baseline for tail-flick and hot plate tests   (MGI Ref ID J:112641)

Pcsk2tm1Dfs/Pcsk2tm1Dfs

        involves: 129S1/Sv * 129X1/SvJ
  • mortality/aging
  • *normal* mortality/aging
    • mice exhibit normal survival in LPS-induced endotoxin shock   (MGI Ref ID J:184882)
  • homeostasis/metabolism phenotype
  • *normal* homeostasis/metabolism phenotype
    • mice exhibit normal response to LPS-induced endotoxin shock   (MGI Ref ID J:184882)
View Research Applications

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

Pcsk2tm1Dfs related

Diabetes and Obesity Research
Hypoinsulinemia
Impaired Insulin Processing

Endocrine Deficiency Research
Pancreas Defects

Metabolism Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Pcsk2tm1Dfs
Allele Name targeted mutation 1, Donald Steiner
Allele Type Targeted (knock-out)
Common Name(s) PC2-; PC2KO; SPC2-;
Mutation Made ByDr. Donald Steiner,   University of Chicago
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line NameR1
ES Cell Line Strain(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Pcsk2, proprotein convertase subtilisin/kexin type 2
Chromosome 2
Gene Common Name(s) 6330411F23Rik; AI839700; NEC 2; NEC-2; NEC2; Nec-2; Nec2; PC2; Phpp-2; RIKEN cDNA 6330411F23 gene; SPC2; expressed sequence AI839700; neuroendocrine convertase 2; prehormone processing proteinase; prohormone convertase 2;
Molecular Note A neomycin resistance cassette was inserted into exon 3, which encodes the activation site at the junction of the propeptide and mature enzyme. RT-PCR experiments demonstrated that exon 3 was absent from transcripts produced from this allele, but Western blot analysis revealed the presence of a truncated protein of a size predicted by this mutation. However, no mature processed protein was detected and there was no evidence of enzyme activity in homozygous mice. [MGI Ref ID J:41505]

Genotyping

Genotyping Information

Genotyping Protocols

Pcsk2tm1Dfs, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Furuta M; Yano H; Zhou A; Rouille Y; Holst JJ; Carroll R; Ravazzola M ; Orci L ; Furuta H ; Steiner DF. 1997. Defective prohormone processing and altered pancreatic islet morphology in mice lacking active SPC2. Proc Natl Acad Sci U S A 94(13):6646-51. [PubMed: 9192619]  [MGI Ref ID J:41505]

Additional References

Furuta M; Carroll R; Martin S; Swift HH; Ravazzola M; Orci L; Steiner DF. 1998. Incomplete processing of proinsulin to insulin accompanied by elevation of Des-31,32 proinsulin intermediates in islets of mice lacking active PC2. J Biol Chem 273(6):3431-7. [PubMed: 9452465]  [MGI Ref ID J:45717]

Miller R; Aaron W; Toneff T; Vishnuvardhan D; Beinfeld MC; Hook VY. 2003. Obliteration of alpha-melanocyte-stimulating hormone derived from POMC in pituitary and brains of PC2-deficient mice. J Neurochem 86(3):556-63. [PubMed: 12859669]  [MGI Ref ID J:84637]

Rehfeld JF; Lindberg I; Friis-Hansen L. 2002. Progastrin processing differs in 7B2 and PC2 knockout animals: a role for 7B2 independent of action on PC2. FEBS Lett 510(1-2):89-93. [PubMed: 11755537]  [MGI Ref ID J:73621]

Pcsk2tm1Dfs related

Beinfeld MC; Blum A; Vishnuvardhan D; Fanous S; Marchand JE. 2005. Cholecystokinin levels in prohormone convertase 2 knock-out mouse brain regions reveal a complex phenotype of region-specific alterations. J Biol Chem 280(46):38410-5. [PubMed: 16174778]  [MGI Ref ID J:103825]

Berman Y; Mzhavia N; Polonskaia A; Furuta M; Steiner DF; Pintar JE; Devi LA. 2000. Defective prodynorphin processing in mice lacking prohormone convertase PC2. J Neurochem 75(4):1763-70. [PubMed: 10987860]  [MGI Ref ID J:126657]

Croissandeau G; Wahnon F; Yashpal K; Seidah NG; Coderre TJ; Chretien M; Mbikay M. 2006. Increased stress-induced analgesia in mice lacking the proneuropeptide convertase PC2. Neurosci Lett 406(1-2):71-5. [PubMed: 16905251]  [MGI Ref ID J:112641]

Fujita Y; Asadi A; Yang GK; Kwok YN; Kieffer TJ. 2010. Differential processing of pro-glucose-dependent insulinotropic polypeptide in gut. Am J Physiol Gastrointest Liver Physiol 298(5):G608-14. [PubMed: 20185691]  [MGI Ref ID J:159247]

Furuta M; Carroll R; Martin S; Swift HH; Ravazzola M; Orci L; Steiner DF. 1998. Incomplete processing of proinsulin to insulin accompanied by elevation of Des-31,32 proinsulin intermediates in islets of mice lacking active PC2. J Biol Chem 273(6):3431-7. [PubMed: 9452465]  [MGI Ref ID J:45717]

Furuta M; Zhou A; Webb G; Carroll R; Ravazzola M; Orci L; Steiner DF. 2001. Severe defect in proglucagon processing in islet A-cells of prohormone convertase 2 null mice. J Biol Chem 276(29):27197-202. [PubMed: 11356850]  [MGI Ref ID J:120493]

Grigoryan M; Kedees MH; Guz Y; Teitelman G. 2012. Phenotype of entero-endocrine L cells becomes restricted during development. Dev Dyn 241(12):1986-92. [PubMed: 23027401]  [MGI Ref ID J:191140]

Hardiman A; Friedman TC; Grunwald WC Jr; Furuta M; Zhu Z; Steiner DF; Cool DR. 2005. Endocrinomic profile of neurointermediate lobe pituitary prohormone processing in PC1/3- and PC2-Null mice using SELDI-TOF mass spectrometry. J Mol Endocrinol 34(3):739-51. [PubMed: 15956344]  [MGI Ref ID J:112500]

Kedees MH; Grigoryan M; Guz Y; Teitelman G. 2009. Differential expression of glucagon and glucagon-like peptide 1 receptors in mouse pancreatic alpha and beta cells in two models of alpha cell hyperplasia. Mol Cell Endocrinol 311(1-2):69-76. [PubMed: 19647035]  [MGI Ref ID J:154947]

Kedees MH; Guz Y; Vuguin PM; Vargas C; Cui L; Steiner DF; Charron MJ; Teitelman G. 2007. Nestin expression in pancreatic endocrine and exocrine cells of mice lacking glucagon signaling. Dev Dyn 236(4):1126-1133. [PubMed: 17366624]  [MGI Ref ID J:119468]

Laurent V; Jaubert-Miazza L; Desjardins R; Day R; Lindberg I. 2004. Biosynthesis of proopiomelanocortin-derived peptides in prohormone convertase 2 and 7B2 null mice. Endocrinology 145(2):519-28. [PubMed: 14576186]  [MGI Ref ID J:88673]

Laurent V; Kimble A; Peng B; Zhu P; Pintar JE; Steiner DF; Lindberg I. 2002. Mortality in 7B2 null mice can be rescued by adrenalectomy: involvement of dopamine in ACTH hypersecretion. Proc Natl Acad Sci U S A 99(5):3087-92. [PubMed: 11854475]  [MGI Ref ID J:126986]

Miller R; Aaron W; Toneff T; Vishnuvardhan D; Beinfeld MC; Hook VY. 2003. Obliteration of alpha-melanocyte-stimulating hormone derived from POMC in pituitary and brains of PC2-deficient mice. J Neurochem 86(3):556-63. [PubMed: 12859669]  [MGI Ref ID J:84637]

Miller R; Toneff T; Vishnuvardhan D; Beinfeld M; Hook VY. 2003. Selective roles for the PC2 processing enzyme in the regulation of peptide neurotransmitter levels in brain and peripheral neuroendocrine tissues of PC2 deficient mice. Neuropeptides 37(3):140-8. [PubMed: 12860111]  [MGI Ref ID J:119037]

Minokadeh A; Funkelstein L; Toneff T; Hwang SR; Beinfeld M; Reinheckel T; Peters C; Zadina J; Hook V. 2010. Cathepsin L participates in dynorphin production in brain cortex, illustrated by protease gene knockout and expression. Mol Cell Neurosci 43(1):98-107. [PubMed: 19837164]  [MGI Ref ID J:158324]

Ni XP; Pearce D; Butler AA; Cone RD; Humphreys MH. 2003. Genetic disruption of gamma-melanocyte-stimulating hormone signaling leads to salt-sensitive hypertension in the mouse. J Clin Invest 111(8):1251-8. [PubMed: 12697744]  [MGI Ref ID J:82967]

Peinado JR; Laurent V; Lee SN; Peng BW; Pintar JE; Steiner DF; Lindberg I. 2005. Strain-dependent influences on the hypothalamo-pituitary-adrenal axis profoundly affect the 7B2 and PC2 null phenotypes. Endocrinology 146(8):3438-44. [PubMed: 15878971]  [MGI Ref ID J:129821]

Refaie S; Gagnon S; Gagnon H; Desjardins R; D'Anjou F; D'Orleans-Juste P; Zhu X; Steiner DF; Seidah NG; Lazure C; Salzet M; Day R. 2012. Disruption of proprotein convertase 1/3 (PC1/3) expression in mice causes innate immune defects and uncontrolled cytokine secretion. J Biol Chem 287(18):14703-17. [PubMed: 22396549]  [MGI Ref ID J:184882]

Rehfeld JF; Lindberg I; Friis-Hansen L. 2002. Progastrin processing differs in 7B2 and PC2 knockout animals: a role for 7B2 independent of action on PC2. FEBS Lett 510(1-2):89-93. [PubMed: 11755537]  [MGI Ref ID J:73621]

Ugleholdt R; Poulsen ML; Holst PJ; Irminger JC; Orskov C; Pedersen J; Rosenkilde MM; Zhu X; Steiner DF; Holst JJ. 2006. Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor. J Biol Chem 281(16):11050-7. [PubMed: 16476726]  [MGI Ref ID J:112681]

Villeneuve P; Feliciangeli S; Croissandeau G; Seidah NG; Mbikay M; Kitabgi P; Beaudet A. 2002. Altered processing of the neurotensin/neuromedin N precursor in PC2 knock down mice: a biochemical and immunohistochemical study. J Neurochem 82(4):783-93. [PubMed: 12358783]  [MGI Ref ID J:78623]

Vincent M; Guz Y; Rozenberg M; Webb G; Furuta M; Steiner D; Teitelman G. 2003. Abrogation of protein convertase 2 activity results in delayed islet cell differentiation and maturation, increased alpha-cell proliferation, and islet neogenesis. Endocrinology 144(9):4061-9. [PubMed: 12933680]  [MGI Ref ID J:85590]

Vishnuvardhan D; Connolly K; Cain B; Beinfeld MC. 2000. PC2 and 7B2 null mice demonstrate that PC2 is essential for normal pro-CCK processing. Biochem Biophys Res Commun 273(1):188-91. [PubMed: 10873584]  [MGI Ref ID J:62889]

Wang J; Xu J; Finnerty J; Furuta M; Steiner DF; Verchere CB. 2001. The prohormone convertase enzyme 2 (PC2) is essential for processing pro-islet amyloid polypeptide at the NH2-terminal cleavage site. Diabetes 50(3):534-9. [PubMed: 11246872]  [MGI Ref ID J:78535]

Webb GC; Akbar MS; Zhao C; Swift HH; Steiner DF. 2002. Glucagon replacement via micro-osmotic pump corrects hypoglycemia and alpha-cell hyperplasia in prohormone convertase 2 knockout mice. Diabetes 51(2):398-405. [PubMed: 11812747]  [MGI Ref ID J:74302]

Zhang X; Pan H; Peng B; Steiner DF; Pintar JE; Fricker LD. 2010. Neuropeptidomic analysis establishes a major role for prohormone convertase-2 in neuropeptide biosynthesis. J Neurochem 112(5):1168-79. [PubMed: 19968759]  [MGI Ref ID J:159031]

Zhu X; Cao Y; Voogd K; Steiner DF. 2006. On the processing of proghrelin to ghrelin. J Biol Chem 281(50):38867-70. [PubMed: 17050541]  [MGI Ref ID J:117652]

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 & HusbandryThis strain is currently being maintained heterozygous sibling matings. Homozygous breeder pairs have a low reproductive performance. Expected coat color from breeding:Black, White Bellied Agouti

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* $2450.00
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* $3185.00
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).

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
   101045 B6129SF2/J (approximate)
 
  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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