Overview

Also Known As: CPP32-

Brain development in Casp3-deficient mice shows a variety of hyperplasias and disorganized cell deployment, and ovaries from female homozygotes show aberrant development. These mutant mice may be useful in studies of apoptosis, ovarian follicle and corpus luteum development, and eye and ear development

Donating Investigator

Dr. Richard A. Flavell, Yale University School of Medicine

Genetic overview

Genetic Background	Generation
	N10+N3F1 (2019-10-03 00:00:00)

Casp3^tm1Flv

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Casp3	caspase 3

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Research Applications

Reproductive Biology Research
Developmental Biology Research
Immunology, Inflammation and Autoimmunity Research
Cardiovascular Research
Research Tools
Sensorineural Research
Mouse/Human Gene Homologs
Apoptosis Research

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Base Price

Starting at:

$255.00 Domestic price for female

333.51 Domestic price for breeder pair

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Details

Detailed Description

On this C57BL/6 congenic background, homozygotes are viable, fertile, and reach adulthood, but females reported display suboptimal mothering instincts. Functional endogenous protein and mRNA are absent from all tissues tested. Homozygous mice are resistant to in vivo cerebral ischemia/reperfusion and in vitro oxygen-glucose deprivation. Ovaries from female homozygotes show aberrant atretic follicles associated with a granulosa cell-intrinsic defect in apoptosis as well as defective corpus luteum regression. Homozygous mice are congenitally deaf with hair cell defects in the Organ of Corti. Optic lens formation/morphology also is abnormal with cataracts at the anterior lens pole. Of note, these mice lack the embryonic/perinatal-lethal brain pathology observed in mutant mice on the 129 and mixed B6;129 genetic backgrounds. These mutant mice may be useful in studies of apoptosis, ovarian follicle and corpus luteum development, and eye and ear development.

Development

A targeting vector was designed to replace the caspase protease-conserved catalytic site of the endogenous gene with a PGK-neo cassette. The construct was electroporated into 129S1/Sv-derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts, and the resulting chimeric males were bred to C57BL/6 females. Heterozygous mice were backcrossed to C57BL/6 mice for ten generations (see SNP results below) prior to sending females and males to The Jackson Laboratory Repository in 2006. Upon arrival, these females and males were used to establish our living mouse colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be C57BL/6N allele-type. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background, the living colony is on a C57BL/6N genetic background, and the sperm frozen in 2008 is on a C57BL/6N genetic background.

Control Suggestions

005304 C57BL/6NJ

Additional Information

Considerations for Choosing Controls

Selected References

Kuida K; Zheng TS; Na S; Kuan C; Yang D; Karasuyama H; Rakic P; Flavell RA. 1996. Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature 384(6607):368-72PubMed: 8934524 MGI: J:36821

View All References

Genetics

Casp3^tm1Flv

Allele Symbol: Casp3^tm1Flv

Allele Name	targeted mutation 1, Richard Flavell
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	targeted mutation 1, Richard Flavell; Casp3^tm1Flv
Gene Symbol and Name	Casp3, caspase 3
Gene Synonym(s)	mldy; Caspase-3; CPP32B; Yama; Apopain; A830040C14Rik; mldy; melody; CC3; SCA-1; CPP32; AC-3; A830040C14Rik; RIKEN cDNA A830040C14 gene; Lice; CPP32-beta
Strain of Origin	129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Chromosome	8
Molecular Note	A genomic fragment containing sequences encoding a conserved motif was replaced with a neomycin selection cassette. RT-PCR analysis on samples derived from brain and liver of homozygous mice demonstrated that no detectable transcript is produced from this allele. Western blot analysis on samples derived from thymocytes of homozygous mice confirmed that no detectable protein was produced.
Mutations Made By	Dr. Richard Flavell, Yale University School of Medicine

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Reproductive Biology Research
- Developmental Defects Affecting Gonads
Developmental Biology Research
- Internal/Organ Defects
  - ovary; uterus
- Eye Defects
Immunology, Inflammation and Autoimmunity Research
- Intracellular Signaling Molecules
Cardiovascular Research
- Ischemia studies
Research Tools
- Reproductive Biology Research
- Apoptosis Research
Sensorineural Research
- Cataracts
- Hearing Defects
- Eye Defects
Mouse/Human Gene Homologs
- deafness
Apoptosis Research
- Endogenous Regulators

Mammalian Phenotype Terms by Genotype

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

Genotype: Casp3^tm1Flv/Casp3^tm1Flv
involves: 129S1/Sv * C57BL/6

cardiovascular system phenotype

abnormal blood vessel morphology
- delayed regression of vitreal vasculature, however the heart is histologically normal

immune system phenotype

abnormal bone marrow development
- increased replicative senescence in bone marrow stromal stem cells from attenuated cell cycle

abnormal osteoclast physiology
- osteoclast activity is reduced, most likely due to dysfunctional preosteoblastic cells

decreased thymocyte number
- fewer total thymocytes at 2 weeks of age, however the spleen is histologically normal

mammalian phenotype

cellular phenotype
- Normal - E12.5 primary telencephalic cultures undergo normal cell death in response to AraC treatment
- Normal - normal phosphatidyl serine flip-flop in thymocytes treated with dexamethasone

immune system phenotype
- Normal - normal thymocyte expression patterns of CD4, CD8, CD25, CD69, and heat stable antigen

nervous system phenotype
- Normal - normal cell number and apoptotic kinetics within the retinal ganglion cell layer and normal width of the nerve fiber and plexiform layers

renal/urinary system phenotype
- Normal - kidney is histologically normal

reproductive system phenotype
- Normal - testis is histologically normal

respiratory system phenotype
- Normal - lung is histologically normal

vision/eye phenotype
- Normal - normal cell number and apoptotic kinetics within the retinal ganglion cell layer and normal width of the nerve fiber and plexiform layers

cellular phenotype

decreased apoptosis
- however, thymocytes show normal susceptibility to apoptosis
- pyknotic clusters at sites of major morphogenetic change during brain development are not observed, indicating a decrease in apoptosis in the brain

mortality/aging

postnatal lethality, complete penetrance
- Background Sensitivity - animals surviving to birth die between 1-3 weeks of age

prenatal lethality, incomplete penetrance
- incomplete penetrance with only 7% homozygous offspring from heterozygote x heterozygote breeders

nervous system phenotype

abnormal brain morphology
- multiple indentations and ectopic cell masses in the cerebrum mantel
- protrusion of brain tissue from the skull at the frontal bone area

abnormal brainstem morphology
- increase in cell number and density of the brainstem at E12

abnormal cerebellar granule layer morphology
- thickness of the internal granular layer is increased

abnormal cerebellar molecular layer
- numerous spindle-shaped granule cells are seen traversing the molecular layer

abnormal cerebellum development
- the germinal layer is thick and mitotically active at P16, at a time when it is normally absent, and spindle-shaped granule cells traverse the molecular layer

abnormal cerebellum external granule cell layer morphology
- the germinal layer is thick and mitotically active at P16, at a time when it is normally absent

abnormal diencephalon morphology
- thicker diencephalic wall with supernumerary cell masses is seen at E12

abnormal forebrain morphology
- ectopic cell masses are found between the cerebral cortex, the hippocampus and the striatum

hydrocephaly
- diencephalic lumen is frequently obstructed at E17

pigmentation phenotype

abnormal retinal pigment epithelium morphology
- absence of the retinal pigment epithelium in a region encircling the optic nerve

skeleton phenotype

abnormal bone ossification
- reduced bone volume to tissue volume ratio
- reduced trabecular thickness

abnormal osteoclast physiology
- osteoclast activity is reduced, most likely due to dysfunctional preosteoblastic cells

abnormal sagittal suture morphology
- open sagittal suture of anterior frontal bone at 7 weeks of age

abnormal skeleton development
- skeleton is smaller than normal at 1 week of age

cranioschisis
- either completely open sagittal suture or incomplete closure at 7 weeks of age

decreased trabecular bone thickness

delayed bone ossification
- evident at E14.5 in skull, metacarpi, phalanges, and sternum and at E17.5 in interparietal bones and metatarsi

craniofacial phenotype

abnormal sagittal suture morphology
- open sagittal suture of anterior frontal bone at 7 weeks of age

cranioschisis
- either completely open sagittal suture or incomplete closure at 7 weeks of age

vision/eye phenotype

abnormal eye development
- delayed regression of vitreal vasculature

abnormal eye morphology
- protrusions of the neuroepithelium in the retina, causing compression on the lens

abnormal optic stalk morphology
- optic stalk contains fewer pyknotic cells and is much larger than in wild-type

abnormal retina morphology
- in severe cases, the posterior retina is folded and elevated at the optic nerve head
- retinal dysplasia near the optic nerve ranging from absence of retinal pigment epithelium to whorled and folded neuroretina

abnormal retinal inner nuclear layer morphology
- delayed apoptotic kinetics result in thickened inner nuclear layer at 5 days of age which resolves after 13 days of age

abnormal retinal pigment epithelium morphology
- absence of the retinal pigment epithelium in a region encircling the optic nerve

microphthalmia
- eyes are 85% to 90% smaller than those of heterozygotes or wild-type

endocrine/exocrine gland phenotype

decreased thymocyte number
- fewer total thymocytes at 2 weeks of age, however the spleen is histologically normal

growth/size/body region phenotype

decreased body size
- smaller than littermates

hematopoietic system phenotype

abnormal osteoclast physiology
- osteoclast activity is reduced, most likely due to dysfunctional preosteoblastic cells

decreased thymocyte number
- fewer total thymocytes at 2 weeks of age, however the spleen is histologically normal

Genotype: Casp3^tm1Flv/Casp3⁺
involves: 129S1/Sv * C57BL/6J

craniofacial phenotype

abnormal sagittal suture morphology
- incomplete closure of sagittal suture of anterior frontal bone at 7 weeks of age

cranioschisis

skeleton phenotype

abnormal bone ossification
- impaired osteogenic differentiation
- reduced bone marrow density
- reduced trabecular thickness at 3 weeks of age

abnormal bone remodeling

abnormal sagittal suture morphology
- incomplete closure of sagittal suture of anterior frontal bone at 7 weeks of age

cranioschisis

decreased bone mineral density
- decreased bone mineral density with age with onset beginning at 3 weeks of age

The following phenotype relates to a compound genotype created using this strain

Genotype: Casp3^tm1Flv/Casp3^tm1Flv
B6.129S1-Casp3

cellular phenotype

abnormal apoptosis
- hemorrhagic response and destruction of the hepatic enothelium and subsequent death in response to injection with anti-Fas antibody Jo2 are delayed at least 12 hours relative to that in wildtype mice and the apoptotic pathway aberrently involves activation, but not altered expression, of caspases 2, 6, and 7
- n, but not altered expression, of caspases 2, 6, and 7

decreased fibroblast apoptosis
- following UV irradiation and staurosporine treatment, mouse embryonic fibroblasts (MEFs) exhibit increased survival compared to wild type MEFs but not as much as Casp7^tm1Flv MEFs

decreased sensitivity to induced cell death
- mouse embryonic fibroblasts treated to initiate apoptosis fail to exhibit DNA fragmentation

mammalian phenotype

reproductive system phenotype
- Background Sensitivity - normal fertility and viable for more than 6 months
- Normal - normal oocyte apoptosis
- Normal - normal ovarian architecture with normal numbers of nonatretic primordial, primary, and small preantral follicles

vision/eye phenotype
- Normal - the size of the lens organelle free zone is normal

nervous system phenotype

abnormal outer hair cell stereociliary bundle morphology

cochlear ganglion degeneration
- at 5 weeks of age neurons are lost from the basal spiral ganglion

cochlear inner hair cell degeneration
- at 5 weeks of age degeneration of inner hair cells is apparent with only 1 row of inner hair cells present in the apical to middle turn

cochlear outer hair cell degeneration
- at 5 weeks of age degeneration of outer hair cells is apparent with only 3 rows of outer hair cells present in the apical to middle turn

fused outer hair cell stereocilia
- at 2 weeks of age there is fusion of stereocilia and at 5 weeks of age all outer hair cell stereocilia are fused at the tips to an unidentified V shaped object

reproductive system phenotype

abnormal granulosa cell morphology
- granulosa cells of atretic follicles are not eliminated by apoptosis and when cultured in the absence of serum fail to complete nuclear fragmentation after initial DNA condensation

abnormal ovarian follicle morphology
- shrunken and disorganized atretic follicles lacking blood cell infiltration

vision/eye phenotype

abnormal lens development
- slight reduction in lysis of fluorogenic substrate DEVD-AMC in both the core and cortex of the lens

abnormal lens epithelium morphology
- the epithelium at the anterior lens pole is multilayered and disorganized and the lens capsule above the opaque region has irregular folds

cataract
- marked cataracts on the optic acis due to accumulation of epithelial cells at the anterior pole of the lens evident by the end of the first postnatal week, mature by 3 weeks of age, but most 6 month to 2 year old homozygotes no longer have cataracts

endocrine/exocrine gland phenotype

abnormal granulosa cell morphology
- granulosa cells of atretic follicles are not eliminated by apoptosis and when cultured in the absence of serum fail to complete nuclear fragmentation after initial DNA condensation

abnormal ovarian follicle morphology
- shrunken and disorganized atretic follicles lacking blood cell infiltration

hearing/vestibular/ear phenotype

abnormal auditory brainstem response waveform shape
- ABR analysis at 2 weeks of age shows atypical waves at all frequencies with sound pressures above 70 dB

abnormal ear morphology

abnormal organ of Corti morphology
- hyperplasia and stratified arrangement of border cells throughout all turns of the cochlea at 2 and 5 weeks of age
- the greater epithelial ridge persists at 2 weeks of age throughout all turns of the cochlea
- the tunnel of Corti and other pericellular spaces are collapsed at 5 weeks of age

abnormal outer hair cell stereociliary bundle morphology

cochlear degeneration

cochlear inner hair cell degeneration
- at 5 weeks of age degeneration of inner hair cells is apparent with only 1 row of inner hair cells present in the apical to middle turn

cochlear outer hair cell degeneration
- at 5 weeks of age degeneration of outer hair cells is apparent with only 3 rows of outer hair cells present in the apical to middle turn

deafness

fused outer hair cell stereocilia
- at 2 weeks of age there is fusion of stereocilia and at 5 weeks of age all outer hair cell stereocilia are fused at the tips to an unidentified V shaped object

increased or absent threshold for auditory brainstem response
- at 5 weeks of age no significant waves are detected even at 100 dB

Genotype: Casp3^tm1Flv/Casp3⁺
B6.129S1-Casp3

mammalian phenotype

hearing/vestibular/ear phenotype
- Normal - hearing and cochlear morphology normal

Genotype: Casp3^tm1Flv/Casp3^tm1Flv
B6N.129S1-Casp3/J

cardiovascular system phenotype

increased cardiomyocyte apoptosis
- in mice treated with doxorubicin

muscle phenotype

increased cardiomyocyte apoptosis
- in mice treated with doxorubicin

cellular phenotype

decreased keratinocyte apoptosis
- mice exhibit decreased sunburn cells with reduced apoptotic keratinocytes generated by UV-B in the skin compared with wild-type mice

increased cardiomyocyte apoptosis
- in mice treated with doxorubicin

increased cellular sensitivity to ultraviolet irradiation
- mice exhibit decreased sunburn cells with reduced apoptotic keratinocytes generated by UV-B in the skin compared with wild-type mice
- mice exposed to UV-B radiation exhibit increased cell death (apoptotic and necrosis-like combined) compared with wild-type mice
- mice exposed to UV-B radiation exhibit increased keratinocytes undergoing necrosis-like death compared with wild-type mice

increased sensitivity to induced cell death
- in the cardiomyocytes of mice treated with doxorubicin

integument phenotype

abnormal keratinocyte physiology
- mice exposed to UV-B radiation exhibit increased keratinocytes undergoing necrosis-like death compared with wild-type mice

decreased keratinocyte apoptosis
- mice exhibit decreased sunburn cells with reduced apoptotic keratinocytes generated by UV-B in the skin compared with wild-type mice

References

Kuida K; Zheng TS; Na S; Kuan C; Yang D; Karasuyama H; Rakic P; Flavell RA. 1996. Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature 384(6607):368-72PubMed: 8934524 MGI: J:36821

Additional - Casp3^tm1Flv related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Casp3^tm1Flv
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

When maintaining a live colony, heterozygous females are bred with either heterozygous or homozygous males. The donating investigator reports that homozygous females are poor mothers.
- Additional Breeding and Husbandry Support
Mating System
- Wild-type x Heterozygote
- Heterozygote x Wild-type
Citation
When using the CPP32- mouse strain in a publication, please cite the originating article(s) and include JAX stock #006233 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

FGB29 (Standard)

Pricing & Availability

Available

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International

Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous for Casp3<tm1Flv>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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.

Related Products and Services

Frozen Mouse Embryo	B6N.129S1-Casp3<tm1Flv>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6N.129S1-Casp3<tm1Flv>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6N.129S1-Casp3<tm1Flv>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6N.129S1-Casp3<tm1Flv>/J Frozen Embryo	$3373.50

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Also Known As: CPP32-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Casp3tm1Flv

Allele Symbol: Casp3tm1Flv

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Casp3tm1Flv/Casp3tm1Flvinvolves: 129S1/Sv * C57BL/6

cardiovascular system phenotype

immune system phenotype

mammalian phenotype

cellular phenotype

mortality/aging

nervous system phenotype

pigmentation phenotype

skeleton phenotype

craniofacial phenotype

vision/eye phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

hematopoietic system phenotype

Genotype: Casp3tm1Flv/Casp3+involves: 129S1/Sv * C57BL/6J

craniofacial phenotype

skeleton phenotype

Genotype: Casp3tm1Flv/Casp3tm1FlvB6.129S1-Casp3

cellular phenotype

mammalian phenotype

nervous system phenotype

reproductive system phenotype

vision/eye phenotype

endocrine/exocrine gland phenotype

hearing/vestibular/ear phenotype

Genotype: Casp3tm1Flv/Casp3+B6.129S1-Casp3

mammalian phenotype

Genotype: Casp3tm1Flv/Casp3tm1FlvB6N.129S1-Casp3/J

cardiovascular system phenotype

muscle phenotype

cellular phenotype

integument phenotype

References

Additional - Casp3tm1Flv related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Casp3^tm1Flv

Allele Symbol: Casp3^tm1Flv

Genotype: Casp3^tm1Flv/Casp3^tm1Flv
involves: 129S1/Sv * C57BL/6

Genotype: Casp3^tm1Flv/Casp3⁺
involves: 129S1/Sv * C57BL/6J

Genotype: Casp3^tm1Flv/Casp3^tm1Flv
B6.129S1-Casp3

Genotype: Casp3^tm1Flv/Casp3⁺
B6.129S1-Casp3

Genotype: Casp3^tm1Flv/Casp3^tm1Flv
B6N.129S1-Casp3/J

Additional - Casp3^tm1Flv related