Strain Detail Sheet

Strain Name:
B6.129-Prkacatm2Gsm/Mmmh
Stock Number:
034324-MU
Citation ID:
RRID:MMRRC_034324-MU

Strain Information

Gene Details

Prkacatm2Gsm
Name: protein kinase, cAMP dependent, catalytic, alpha; targeted mutation 2, G Stanley McKnight
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 8
Alteration at locus: Targeted Mutation
Prkaca
Name: protein kinase, cAMP dependent, catalytic, alpha
Synonyms: Cs, C alpha, PKA, Pkaca
Type: Gene
Species: Mouse
Chromosome: 8
Alteration at locus: Targeted Mutation
NCBI: 18747
HGNC: HGNC:9380
Homologene: 121574
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Genetic Alterations
Targeted Disruption of Prkaca. Prkaca null mice were generated from the targeted disruption of exon 1b of the Prkaca gene by homologous recombination in embryonic stem (ES) cells. The targeting vector was constructed from a 13.2-kb genomic fragment containing exons 1-3 of Prkaca. A loxP-flanked neomycin phosphotransferase(NEO) cassette and a mutation of the translational initiation codon were inserted into exon 1b. The linearized targeting vector was electroporated into ES cells derived from129SV/J mice as described. Germ-line chimeras were bredto C57BL/6 mice. Pups carrying the NEO were crossed to heterozygous ROSA26-Cre recombinase transgenic mice (from P. Sorriano, Fred Hutchinson Cancer Research Center, Seattle) to remove the NEO. Subsequent backcrossing and selection of ROSA26-Cre-negative mice generated Prkacatm2Gsm heterozygote mutant.
Genotype Determination
ES Cell Line
R1 derived from (129X1/SvJ x 129S1/Sv)F1-Kitl+

Strain Description

Phenotype
Homozygous: Prkacatm2Gsm is a unique splice variant of the Prkaca gene encoded by a single 5' exon 1b that is expressed uniquely in developing male sperm at the pachytene stage onward; when Prkacatm2Gsm comes on, the somatic exon 1a Calpha splice variant is replaced by the exon 1b Prkacatm2Gsm splice variant. Male Prkacatm2Gsm null mice produce normal numbers of sperm that swim spontaneously in vitro. Thus, Prkacatm2Gsm has no required role in formation of a functional flagellum or the initiation of motility. In contrast, we find that Prkacatm2Gsm is required for bicarbonate to speed the flagellar beat and facilitate Ca2+ entry channels. In addition, Prkacatm2Gsm is needed for the protein tyrosine phosphorylation that occurs late in the sequence of sperm maturation and for a negative feedback control of cAMP production, revealed here. Consistent with these specific defects in several important sperm functions, Prkacatm2Gsm null males are infertile despite normal mating behavior. These results define several crucial roles of PKA in sperm cell biology, bringing together both known and unique PKA-

Heterozygous: Prkacatm2Gsm heterozygous mice, both male and female, are viable and fertile and live a normal lifespan.
Mammalian Phenotype Terms
Allelic Composition: Prkacatm2Gsm/Prkacatm2Gsm (Genetic Background: involves: 129X1/SvJ * C57BL/6 )
MeSH Terms
  • Adenylyl Cyclases/metabolism
  • Animals
  • Bicarbonates/pharmacology
  • Calcium/metabolism
  • Catalysis
  • Cyclic AMP/biosynthesis
  • Cyclic AMP/metabolism
  • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
  • Cyclic AMP-Dependent Protein Kinases/deficiency
  • Cyclic AMP-Dependent Protein Kinases/genetics
  • Cyclic AMP-Dependent Protein Kinases/metabolism
  • Feedback, Physiological
  • Fertility/physiology
  • Gene Deletion
  • Isoenzymes/deficiency
  • Isoenzymes/genetics
  • Isoenzymes/metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Phenotype
  • Signal Transduction
  • Spermatozoa/drug effects
  • Spermatozoa/enzymology
  • Spermatozoa/metabolism
  • Testis/cytology
  • Testis/enzymology
  • Testis/metabolism
  • Alternative Splicing
  • Amino Acid Sequence
  • Base Sequence
  • Catalytic Domain
  • Chromosome Mapping
  • Conserved Sequence
  • Enzyme Activation
  • Humans
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Spermatozoa/physiology
  • Transcription, Genetic
Strain Development
129/SvJ:C57BL/6 chimeric males were bred to wildtype C57BL/6Crl females and F1 offspring identified by southern blot and PCR. Heterozygous F1 offspring were then backcrossed continually to C57BL/6Crl mice to maintain the colony.
Suggested Control Mice

Wildtype littermates

MMRRC Genetic QC

MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact mmrrc@missouri.edu. Older strains may not have this information.

Research Applications

  • Cell Biology
  • Models for Human Disease
  • Reproduction

Strain Origin

Donor
G. Stanley McKnight, Ph.D., University of Washington
Primary Reference
  • Nolan MA; Babcock DF; Wennemuth G; Brown W; Burton KA; McKnight GS, Sperm-specific protein kinase A catalytic subunit Calpha2 orchestrates cAMP signaling for male fertility., Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13483-8 (Medline PMID: 15340140)
  • Desseyn JL, Burton KA, McKnight GS. Expression of a nonmyristylated variant of the catalytic subunit of protein kinase A during male germ-cell development.Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6433-8. (Medline PMID: 10841548)

Colony and Husbandry Information

Special Considerations

Male and female Prkacatm2Gsm mice are viable, healthy and fertile and do not show any unusual phenotypes. Both female and male Prkacatm2Gsm heterozygote mice are maintained and backcrossed to C57BL/6Crl mice regularly to maintain the colony.

Health Status Report

Colony Surveillance Program and Current Health Reports

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@missouri.edu.

Order Request Information

Availability Level

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Cryopreserved material may be available upon request, please inquire to mmrrc@missouri.edu for more information.

Conditions of Distribution

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The donor or their institution limits the distribution to non-profit institutions only.

Fees

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*		 Units Notes
034324-MU-SPERM Cryo-preserved spermatozoa $437.00 / Non-Profit Aliquot Approximate quantity3
034324-MU-RESUS Litter recovered from cryo-archive $2,624.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to mmrrc@missouri.edu for more information.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.