A genomic clone containing the 59 end of the mouse Atp2a2 gene was isolated from a strain 129/SvJ phage library and used to prepare targeting constructs. A neo cassette replaced part of the promoter region and first exon in the Atp2a2 gene, thereby eliminating expression of the transcript.
Homozygous: Embryonic lethal
Heterozygous: Heterozygotes exhibit a reduction in cardiac contractility (SERCA2 is the cardiac SR Ca pump), susceptibility to cardiac disease in response to pressure overload, and a reduced force-frequency response in heart; the most dramatic phenotype is a high incidence of squamous cell tumors of keratinized epithelial tissues (approximately 90%). In humans, SERCA2 heterozygosity causes Darier Disease, a skin condition involving keratinocytes.
The clone containing the Atp2a2 gene was isolated from a strain 129/SvJ phage library. Target vector was transfected by electroportation into ES cells derived from 129X1/SvJ. The selected ES cell lines containing the disrupted Atp2a2 gene were used for blastocyst-mediated transgenesis. The resulting chimeric mice were mated to Black Swiss mice and backcrossed to the FVB/N mice.
Periasamy M, Reed TD, Liu LH, Ji Y, Loukianov E, Paul RJ, Nieman ML, Riddle T, Duffy JJ, Doetschman T, Lorenz JN, Shull GE. Impaired cardiac performance in heterozygous mice with a null mutation in the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 (SERCA2) gene. J Biol Chem. 1999 Jan 22; 274(4): 2556-62. (Medline PMID: 9891028)
Prasad V, Boivin GP, Miller ML, Liu LH, Erwin CR, Warner BW, Shull GE. Haploinsufficiency of Atp2a2, encoding the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 Ca2+ pump, predisposes mice to squamous cell tumors via a novel mode of cancer susceptibility. Cancer Res. 2005 Oct 1;65(19):8655-61. (Medline PMID: 16204033)
Liu LH, Boivin GP, Prasad V, Periasamy M, Shull GE. Squamous cell tumors in mice heterozygous for a null allele of Atp2a2, encoding the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 Ca2+ pump. J Biol Chem. 2001 Jul 20; 276(29): 26737-40. (Medline PMID: 11389134)
Schultz Jel J, Glascock BJ, Witt SA, Nieman ML, Nattamai KJ, Liu LH, Lorenz JN, Shull GE, Kimball TR, Periasamy M. Accelerated onset of heart failure in mice during pressure overload with chronically decreased SERCA2 calcium pump activity. Am J Physiol Heart Circ Physiol. 2004 Mar;286(3):H1146-53. (Medline PMID: 14630633)
Huke S, Liu LH, Biniakiewicz D, Abraham WT, Periasamy M. Altered force-frequency response in non-failing hearts with decreased SERCA pump-level. Cardiovasc Res. 2003 Sep 1;59(3):668-77. (Medline PMID: 14499868)
Zhao XS, Shin DM, Liu LH, Shull GE, Muallem S. Plasticity and adaptation of Ca2+ signaling and Ca2+-dependent exocytosis in SERCA2(+/-) mice. EMBO J. 2001 Jun 1;20(11):2680-9. (Medline PMID: 11387203)
Wild-type (FVB/N) female x Heterozygous male or reciprocal mating.
|Viability and Fertility:||Female||Male||Comments|
|Homozygotes are viable:||No||No|
|Homozygotes are fertile:||N/A||N/A|
|Heterozygotes are fertile:||Yes||Yes||Develop cancer and cardiac phenotypes.|
|Age Reproductive Decline:||Not specified||Not specified|
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.
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.
|MMRRC Item #||Description||Distribution Fee / Unit (US $)
*Shipping & Handling not included*
|036806-JAX-SPERM||Cryo-preserved spermatozoa||$437.00 / Non-Profit||Aliquot||Approximate quantity3|
|036806-JAX-RESUS||Litter recovered from cryo-archive||$2,022.00 / Non-Profit||Litter||Recovered litter4; additional fees for any special requests.|
|Cryopreserved material may be available upon request, please inquire to firstname.lastname@example.org 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.