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| These Sgpl1-mutant mice may be useful in studying cellular signaling in development and adult mice; specifically receptor tyrosine kinases (RTK; such as Ras, MAP kinase, PI3K and those in the platelet-derived growth factor (PDGF) family) and immediate early genes (IEG) induced shortly after RTK activation. Homozygotes exhibit vascular defects, polychromasia, kidney defects and palate bone fusion abnormalities. | |||||||||||||||
- Description
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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 Gene Trap; Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation ?+F0pN1 Donating Investigator Philippe Soriano, Mount Sinai School of Medicine Description
Mice homozygous for this mutant allele have reduced size and weight gains after birth and do not survive past 8 weeks of age. Homozygotes occur at a lower than Mendelian ratio (19%) from heterozygote X heterozygote crosses. No gene product is detected in homozygous embryos aged ED9.5-12.5 or in adult gonad. Beta-galactosidase staining pattern mimics the endogenous gene expression pattern in adult intestinal epithelial cells. Homozygous embryos E11.5 to E18.5 exhibit hemorrhages and microaneurisms. Vascular defects persist into adulthood. At 6 weeks of age, mutant mice are anemic (low hemoglobin concentration, reduced red blood cell count, low hematocrit). Mutants exhibit polychromasia (abnormally high number of immature blood cells), kidney defects (blood urea nitrogen level abnormally high, kidney size smaller than wildtype, swollen blood filled glomeruli, reduced number of vascular smooth muscle cells) and abnormalities in palate bone fusion. Homozygotes are infertile. Heterozygotes are viable and fertile. These Sgpl1-mutant mice may be useful in studying cellular signaling in development and adult mice; specifically receptor tyrosine kinases (RTK; such as Ras, MAP kinase, PI3K and those in the platelet-derived growth factor (PDGF) family) and immediate early genes (IEG) induced shortly after RTK activation.Development
The retroviral gene-trap vector ROSAFARY (or reverse orientation splice acceptor for array) was designed with a promoter trap module (SAβgeo*pA; encoding a lacZ-neo fusion gene) and an frt-flanked poly-A trap module (PGKhygSD; PGK promoter-driven hygromycin gene with adenoviral splice donor). This construct was electroporated into 129S4/SvJaeSor-derived AK7.1 embryonic stem (ES) cells. ES cells with the ROSAFARY vector correctly targeted to the Sgpl1 gene (in the 2nd intron) were identified and used to generate mutant mice. Homozygous mice were maintained on a 129S4/SvJaeSor background prior to arrival at The Jackson Laboratory. The mice were then crossed to 129S1/SvImJ (Stock No. 002448) for one generation.The ROSAFARY vector inserts a promoterless lacZ-neo reporter fusion gene (which functions as an artificial 3' terminal exon to intercept and terminate transcription from the targeted gene promoter) as well as a poly-A trap (which functions as an artificial 5' terminal exon to initiate transcription from the insertion site). After inserting into an intron of an endogenous gene at a permissive site and in the correct orientation, the promoter trap module and the poly-A trap module can be activated to form fusion transcripts with the 5' or 3' exons.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
Related Strains
lacZ Expression Strains
View lacZ Expression Strains (186 strains)
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
assigned by genotype
Sgpl1Gt(ROSA)78Sor/Sgpl1Gt(ROSA)78Sor
involves: 129S4/SvJaeSor
- life span-post-weaning/aging
- premature death (MGI Ref ID J:117491)
- all mice die by 8 weeks
- skeleton phenotype
- abnormal skeleton morphology (MGI Ref ID J:117491)
- abnormal neural crest derived and thoracic skeleton
- abnormal calvaria morphology (MGI Ref ID J:117491)
- 75% of mice have reduced calvarial bones at the midline with increases in the gaps between frontal bones
- abnormal frontal bone morphology (MGI Ref ID J:117491)
- increases in the gaps between frontal bones
- abnormal palatine shelf (MGI Ref ID J:117491)
- 75% of mice have smaller and less extended towards the midline palatine and presphenoid bones
- abnormal presphenoid bone morphology (MGI Ref ID J:117491)
- 75% of mice have smaller and less extended towards the midline palatine and presphenoid bones
- abnormal sternum morphology (MGI Ref ID J:117491)
- 50% of mice have sternum defects including asymmetric or additional fusion of ribs and gaps in the sternum
- asymmetric rib-sternum attachment (MGI Ref ID J:117491)
- abnormal vertebrae morphology (MGI Ref ID J:117491)
- 20% of mice have widened vertebral arches and forked vertebrae
- abnormal vertebral arch morphology (MGI Ref ID J:117491)
- 20% of mice have widened vertebral arches and forked vertebrae
- renal/urinary system phenotype
- abnormal kidney morphology (MGI Ref ID J:117491)
- abnormal renal glomerulus morphology (MGI Ref ID J:117491)
- glomeruli are often degraded
- smooth muscle cell number is reduced in the glomeruli
- migration of smooth muscle cells in glomeruli is impaired
- pale kidney (MGI Ref ID J:117491)
- small kidney (MGI Ref ID J:117491)
- abnormal kidney physiology (MGI Ref ID J:117491)
- decrease in kidney function
- kidney inflammation (MGI Ref ID J:117491)
- kidney is swollen in sections and blood filled
- hematopoietic system phenotype
- abnormal red blood cell (MGI Ref ID J:117491)
- an increase in immature red blood cells is observed compared to wild-type mice
- anemia (MGI Ref ID J:117491)
- by week 6
- decreased erythrocyte cell number (MGI Ref ID J:117491)
- by week 6
- decreased hematocrit (MGI Ref ID J:117491)
- by week 6
- decreased hemoglobin content (MGI Ref ID J:117491)
- by week 6
- polychromatophilia (MGI Ref ID J:117491)
- growth/size phenotype
- decreased body weight (MGI Ref ID J:117491)
- postnatal growth retardation (MGI Ref ID J:117491)
- cellular phenotype
- abnormal cell migration (MGI Ref ID J:117491)
- migration of smooth muscle cells in glomeruli is impaired
- mouse embryonic fibroblast cells show reduced migration in a scratch test in response to PDGF stimulation
- homeostasis/metabolism phenotype
- increased blood urea nitrogen level (MGI Ref ID J:117491)
- cardiovascular system phenotype
- abnormal blood vessel morphology (MGI Ref ID J:117491)
- hemorrhage (MGI Ref ID J:117491)
- at E11.5-E18.5
- muscle phenotype
- abnormal smooth muscle morphology (MGI Ref ID J:117491)
- smooth muscle cell number is reduced in the glomeruli
- immune system phenotype
- kidney inflammation (MGI Ref ID J:117491)
- kidney is swollen in sections and blood filled
- craniofacial phenotype
- abnormal calvaria morphology (MGI Ref ID J:117491)
- 75% of mice have reduced calvarial bones at the midline with increases in the gaps between frontal bones
- abnormal frontal bone morphology (MGI Ref ID J:117491)
- increases in the gaps between frontal bones
- abnormal palate morphology (MGI Ref ID J:117491)
- irregularities in fusion persist into adulthood
- abnormal palatine shelf (MGI Ref ID J:117491)
- 75% of mice have smaller and less extended towards the midline palatine and presphenoid bones
- abnormal presphenoid bone morphology (MGI Ref ID J:117491)
- 75% of mice have smaller and less extended towards the midline palatine and presphenoid bones
- digestive/alimentary phenotype
- abnormal palate morphology (MGI Ref ID J:117491)
- irregularities in fusion persist into adulthood
- abnormal palatine shelf (MGI Ref ID J:117491)
- 75% of mice have smaller and less extended towards the midline palatine and presphenoid bones
Sgpl1Gt(ROSA)78Sor/Sgpl1Gt(ROSA)78Sor
either: (involves: 129S4/SvJaeSor) or (involves: 129S4/SvJaeSor * C57BL/6)
- reproductive system phenotype
- abnormal ovary morphology (MGI Ref ID J:142042)
- ovaries of females older than 8 weeks exhibit a hyperplastic stroma, containing multiple atretic follicles
- reduction in theca cells
- reduction in numbers of vascular smooth muscle cells in the ovaries
- abnormal ovarian follicle number (MGI Ref ID J:142042)
- decreased numbers of later stage antral follicles
- absent corpus luteum (MGI Ref ID J:142042)
- small ovary (MGI Ref ID J:142042)
- abnormal spermatogenesis (MGI Ref ID J:142042)
- at P42, spermatogenesis is absent
- abnormal spermatid morphology (MGI Ref ID J:142042)
- at P42, spermatids are absent
- abnormal spermatocyte morphology (MGI Ref ID J:142042)
- loss of spermatocytes from the testis cords by P42
- abnormal testis morphology (MGI Ref ID J:142042)
- testis morphology appears normal at P7, but by P20 mutants show a reduction in the testis interstitium
- decrease in testosterone levels in testis
- Leydig cell hypoplasia (MGI Ref ID J:142042)
- reduction in Leydig cells before and during early adolescence (P7, P14, P21)
- abnormal testis cord formation (MGI Ref ID J:142042)
- by p20, mutants exhibit gaps in the spermatocyte layers of the testis cords
- at P42, multinucleated giant cells are seen throughout testis cords
- small testis (MGI Ref ID J:142042)
- reduction in testis size is observed by P42
- anovulation (MGI Ref ID J:142042)
- little or no ovulation
- female infertility (MGI Ref ID J:142042)
- male infertility (MGI Ref ID J:142042)
- uterus hypoplasia (MGI Ref ID J:142042)
- uterus is hypoplastic, with major uterine layers present but underdeveloped
- homeostasis/metabolism phenotype
- decreased circulating estradiol level (MGI Ref ID J:142042)
- decreased circulating testosterone level (MGI Ref ID J:142042)
- decrease in testosterone levels in serum and testis
- endocrine/exocrine gland phenotype
- abnormal ovary morphology (MGI Ref ID J:142042)
- ovaries of females older than 8 weeks exhibit a hyperplastic stroma, containing multiple atretic follicles
- reduction in theca cells
- reduction in numbers of vascular smooth muscle cells in the ovaries
- abnormal ovarian follicle number (MGI Ref ID J:142042)
- decreased numbers of later stage antral follicles
- absent corpus luteum (MGI Ref ID J:142042)
- small ovary (MGI Ref ID J:142042)
- abnormal testis morphology (MGI Ref ID J:142042)
- testis morphology appears normal at P7, but by P20 mutants show a reduction in the testis interstitium
- decrease in testosterone levels in testis
- Leydig cell hypoplasia (MGI Ref ID J:142042)
- reduction in Leydig cells before and during early adolescence (P7, P14, P21)
- abnormal testis cord formation (MGI Ref ID J:142042)
- by p20, mutants exhibit gaps in the spermatocyte layers of the testis cords
- at P42, multinucleated giant cells are seen throughout testis cords
- small testis (MGI Ref ID J:142042)
- reduction in testis size is observed by P42
- cardiovascular system phenotype
- abnormal vascular smooth muscle morphology (MGI Ref ID J:142042)
- reduction in numbers of vascular smooth muscle cells in the ovaries
- muscle phenotype
- abnormal vascular smooth muscle morphology (MGI Ref ID J:142042)
- reduction in numbers of vascular smooth muscle cells in the ovaries
This mouse can be used to support research in many areas including:
Cardiovascular Research
Vascular Defects
Cell Biology Research
Signal Transduction
Developmental Biology Research
Craniofacial and Palate Defects
Embryonic Lethality (Homozygous)
Growth Defects
Internal/Organ Defects
kidney
multiple
vasculature
Skeletal Defects
Hematological Research
Hematopoietic Defects
Internal/Organ Research
Kidney Defects
Research Tools
lacZ Expression
Cardiovascular Research
Cell Biology Research
Developmental Biology Research
Genetics Research
Tissue/Cell Markers
Hematological Research
Internal/Organ Research
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Sgpl1Gt(ROSA)78Sor | ||
|---|---|---|---|
| Allele Name | gene trapped 78, Philippe Soriano | ||
| Allele Type | Gene trapped | ||
| Common Name(s) | Sgpl1-; | ||
| Mutation Made By | Philippe Soriano, Mount Sinai School of Medicine | ||
| Strain of Origin | 129S4/SvJaeSor | ||
| ES Cell Line Name | AK7 | ||
| ES Cell Line Strain | 129S4/SvJaeSor | ||
| Site of Expression | lacZ expression pattern mimics the endogenous gene expression pattern in adult intestinal epithelial cells. | ||
| Gene Symbol and Name | Sgpl1, sphingosine phosphate lyase 1 | ||
| Chromosome | 10 | ||
| Gene Common Name(s) | AI428538; D10Xrf456; FLJ13811; KIAA1252; SPL; Spgl1; expressed sequence AI428538; | ||
| Molecular Note | The Rosafary gene trap vector containing a SAbetaGeo pA promoter trap module and a PGKhygSD poly-A trap module was inserted into intron 2. [MGI Ref ID J:117491] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Sgpl1Gt(ROSA)78Sor, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
Schmahl J; Raymond CS; Soriano P. 2007. PDGF signaling specificity is mediated through multiple immediate early genes. Nat Genet 39(1):52-60. [PubMed: 17143286] [MGI Ref ID J:117491]
Additional References
Sgpl1Gt(ROSA)78Sor relatedOskouian B; Sooriyakumaran P; Borowsky AD; Crans A; Dillard-Telm L; Tam YY; Bandhuvula P; Saba JD. 2006. Sphingosine-1-phosphate lyase potentiates apoptosis via p53- and p38-dependent pathways and is down-regulated in colon cancer. Proc Natl Acad Sci U S A 103(46):17384-9. [PubMed: 17090686] [MGI Ref ID J:117131]
Schmahl J; Rizzolo K; Soriano P. 2008. The PDGF signaling pathway controls multiple steroid-producing lineages. Genes Dev 22(23):3255-67. [PubMed: 19056881] [MGI Ref ID J:142042]
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
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice are bred as heterozygotes. Homozygotes are not fertile and die by 8 weeks of age.
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $1900.00 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.
Additional Supply Details
| Pricing for International shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $2470.00 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.
Additional Supply Details
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|
Supply Details
| Standard Supply | Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - 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.Ordering and Purchasing Information
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