Description

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. Mating System Homozygote x Heterozygote         (Female x Male)   26-OCT-12 Species laboratory mouse Generation N17+N1F0 (04-JAN-13) Generation Definitions   Donating Investigator David Clapham,   HHMI/Children's Hospital

Description
CATSPER1 (cation channel, sperm associated 1) is one of four related proteins that combine to form Ca²⁺-permeant ion channels associated with normal sperm cell function. These channels are localized primarily to the tail's principal piece, not the head or midpiece.

Knockouts of the Catsper1 gene produce mice that show no gross phenotype other than male-specific infertility due to a lack of sperm hyperactivation. Homozygous females are fertile. Ca²⁺ current is abolished in the sperm of mutant mice directly measured by whole cell path clamp. The gene is proposed as an excellent target for non-hormonal contraceptives for both men and women.

Development
The second exon, encoding the first putative transmembrane domain, was replaced with an IRES-LacZ sequence followed by a neomycin resistance gene in 129S4/SvJae-derived J1 embryonic stem (ES) cells. Resultant mice were backcrossed to C57BL/6J for more than 17 generations by the donating laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Spermatogenic Failure 7; SPGF7   (CATSPER1)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Catsper1^tm1Clph/Catsper1^tm1Clph

        involves: 129S4/SvJae * C57BL/6J

• reproductive system phenotype
• asthenozoospermia
  • mutant sperm are sluggish, exhibit less directed movements, and lack the vigorous beating and bending in the tail region noted in wild-type sperm   (MGI Ref ID J:72046)
  • major motility parameters, including path velocity, progressive velocity, and track speed, are significantly impaired   (MGI Ref ID J:72046)
• impaired acrosome reaction
  • in vitro, mutant sperm are unable to penetrate the zona pellucida   (MGI Ref ID J:72046)
  • neither cAMP nor cGMP is shown to elicit a significant Ca²⁺ influx in fully differentiated mutant sperm   (MGI Ref ID J:72046)
  • in contrast, progesterone, which is used as a positive control for Ca²⁺ responses, initiates a large Ca²⁺ increase in both mutant and wild-type sperm   (MGI Ref ID J:72046)
• impaired fertilization
  • in vitro, mutant sperm are unable to fertilize eggs with an intact zona pellucida   (MGI Ref ID J:72046)
  • in contrast, mutant sperm are able to fertilize eggs in which the zona pellucida has been removed   (MGI Ref ID J:72046)
• male infertility
  • male homozygotes exhibit normal mounting behavior but are sterile   (MGI Ref ID J:72046)
  • however, mutant males display no significant differences in body and testis weights, spermatogenesis, sperm morphology or sperm counts relative to wild-type littermates   (MGI Ref ID J:72046)
• homeostasis/metabolism phenotype
• abnormal calcium ion homeostasis
  • the cyclic-AMP-induced Ca²⁺ entry in the sperm tail is abolished in mutant sperm   (MGI Ref ID J:72046)

Catsper1^tm1Clph/Catsper1^tm1Clph

        involves: 129S4/SvJae

• reproductive system phenotype
• abnormal sperm physiology
  • calcium-selective pH sensitive sperm current (I_CatSper) is not detectable   (MGI Ref ID J:116406)
• • abnormal sperm motility
    • percent motility of mutant sperm decreases more rapidly than wild-type   (MGI Ref ID J:116406)
  • • asthenozoospermia
      • after 90 minutes in viscous conditions, sperm lose their motility compared to wild-type which move more vigorously than initially   (MGI Ref ID J:116406)

View Research Applications

Research Applications

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

Cell Biology Research
Channel and Transporter Defects
      calcium

Reproductive Biology Research
Fertility Defects
      males only

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Catsper1tm1Clph
Allele Name		targeted mutation 1, David E Clapham
Allele Type		Targeted (knock-out)
Common Name(s)		CatSper-;
Mutation Made By		David Clapham,   HHMI/Children's Hospital
Strain of Origin		129S4/SvJae
Gene Symbol and Name		Catsper1, cation channel, sperm associated 1
Chromosome		19
Gene Common Name(s)		CATSPER; KSper; SPGF7;
Molecular Note		The second exon coding the first putative transmembrane domain was replaced with an IRES-LacZ sequence followed by the neomycin resistance gene. Western blotting confirmed absence of protein from testis of homozygous mutant mice. [MGI Ref ID J:72046]

Genotyping

Genotyping Information

Genotyping Protocols

Catsper1^tm1Clph alternate2,

SEPARATED MELT

Catsper1^tm1Clphalternate2, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Ren D; Navarro B; Perez G; Jackson AC; Hsu S; Shi Q; Tilly JL; Clapham DE. 2001. A sperm ion channel required for sperm motility and male fertility. Nature 413(6856):603-9. [PubMed: 11595941]  [MGI Ref ID J:72046]

Additional References

Catsper1^tm1Clph related

Carlson AE; Quill TA; Westenbroek RE; Schuh SM; Hille B; Babcock DF. 2005. Identical phenotypes of CatSper1 and CatSper2 null sperm. J Biol Chem 280(37):32238-44. [PubMed: 16036917]  [MGI Ref ID J:128548]

Carlson AE; Westenbroek RE; Quill T; Ren D; Clapham DE; Hille B; Garbers DL; Babcock DF. 2003. CatSper1 required for evoked Ca2+ entry and control of flagellar function in sperm. Proc Natl Acad Sci U S A 100(25):14864-8. [PubMed: 14657352]  [MGI Ref ID J:86971]

Ho K; Wolff CA; Suarez SS. 2009. CatSper-null mutant spermatozoa are unable to ascend beyond the oviductal reservoir. Reprod Fertil Dev 21(2):345-50. [PubMed: 19210926]  [MGI Ref ID J:151121]

Marquez B; Ignotz G; Suarez SS. 2007. Contributions of extracellular and intracellular Ca2+ to regulation of sperm motility: Release of intracellular stores can hyperactivate CatSper1 and CatSper2 null sperm. Dev Biol 303(1):214-21. [PubMed: 17174296]  [MGI Ref ID J:118812]

Navarro B; Miki K; Clapham DE. 2011. ATP-activated P2X2 current in mouse spermatozoa. Proc Natl Acad Sci U S A 108(34):14342-7. [PubMed: 21831833]  [MGI Ref ID J:175979]

Qi H; Moran MM; Navarro B; Chong JA; Krapivinsky G; Krapivinsky L; Kirichok Y; Ramsey IS; Quill TA; Clapman DE. 2007. All four CatSper ion channel proteins are required for male fertility and sperm cell hyperactivated motility Proc Natl Acad Sci U S A :. [PubMed: 17227845]  [MGI Ref ID J:116406]

Xia J; Ren D. 2009. Egg coat proteins activate calcium entry into mouse sperm via CATSPER channels. Biol Reprod 80(6):1092-8. [PubMed: 19211808]  [MGI Ref ID J:149683]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & Husbandry	The donating laboratory maintained this strain though crosses of homozygous females with heterozygous males.
Mating System	Homozygote x Heterozygote         (Female x Male)   26-OCT-12
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory's Genotype Promise

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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