Overview

Also Known As:staggerer

Mice homozygous for the staggerer spontaneous mutation (Rora^sg) show a staggering gait, mild tremor, hypotonia, and small size. The cerebellar cortex of homozygous mutant mice is grossly underdeveloped with a deficiency of granule cells and Purkinje cells. The remaining granule cells migrate inward from the external layer prematurely and then degenerate. Purkinje cells are much delayed in postnatal differentiation and lack the dendritic spines on which synapses with the parallel fibers from the granule cells normally occur. Staggerer mutant mice have been used as a source of an agranulate cerebellum in a number of investigations of the composition and function of granule cells. Kopmels et al. have reported a hyperproduction of IL1 biological activity and mRNA from LPS stimulated spleen cells of Rora^sg/Rora^sg mice on the C57BL/6J background relative to wild type siblings.

Genetic overview

Genetic Background	Generation

a

Allele Type	Gene Symbol	Gene Name
Spontaneous	a	nonagouti

Rora^sg

Allele Type	Gene Symbol	Gene Name
Spontaneous	Rora	RAR-related orphan receptor alpha

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Research Applications

Neurobiology Research

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$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the staggerer spontaneous mutation (Rora^sg) show a staggering gait, mild tremor, hypotonia, and small size. The cerebellar cortex of homozygous mutant mice is grossly underdeveloped with a deficiency of granule cells and Purkinje cells. The remaining granule cells migrate inward from the external layer prematurely and then degenerate. Purkinje cells are much delayed in postnatal differentiation and lack the dendritic spines on which synapses with the parallel fibers from the granule cells normally occur. Staggerer mutant mice have been used as a source of an agranulate cerebellum in a number of investigations of the composition and function of granule cells. Kopmels et al. have reported a hyperproduction of IL1 biological activity and mRNA from LPS stimulated spleen cells of Rora^sg/Rora^sg mice on the C57BL/6J background relative to wild type siblings.

Development

The first Rora^sg/Rora^sg mouse was observed in 1955 among the F2 progeny of a (BALB/cHm x C3H/HeJ)F1 female and a male of an obese(Lep^ob) stock of mixed background. The mutation was maintained for several generations by an intercross-backcross (within the same or a parallel lineage) mating scheme, then was backcrossed onto C57BL/6J for four generations. A Rora^sg/+ male from the fourth backcross was mated to a female C57BL/10-Myo5a^d Bmp5^se mouse to introduce the dilute and short-ear mutations into the stock in repulsion with Rora^sg; this allowed the heterozygotes (Rora^sg + +/+ Myo5a^d Bmp5^se to be identified by a lack of either recessive phenotype. Brother-sister inbreeding was continued. In late 1978, at generation F53, a repulsion heterozygote, (Rora^sg + +/+ Myo5a^d Bmp5^se) was outcrossed to a C3FeLe.B6-a/J and two of their Rora^sg heterozygous offspring, which lacked Myo5a^d and Bmp5^se, were intercrossed to generate a homozygous female from which ovaries were transplanted and the host was bred to a B6C3FeF1/J-a/a male. This line was maintained for many years through this 2-generation breeding scheme, with a homozygous ovarian transplant host being bred to a B6C3FeF1/J-a/a male and then intercrossing their obligate Rora^sg heterozygous offspring. In 2003 embryos were generated for cryopreservation from B6C3FeF1/J-a/a females bred to heterozygous males then at generation NE44F1, having been through 44 two-generation breeding cycles of crossing to the F1 hybrid.

Control Suggestions

Untyped from the colony

Additional Information

Considerations for Choosing Controls

Selected References

Mamontova A; Seguret-Mace S; Esposito B; Chaniale C; Bouly M; Delhaye-Bouchaud N; Luc G; Staels B; Duverger N; Mariani J; Tedgui A. 1998. Severe atherosclerosis and hypoalphalipoproteinemia in the staggerer mouse, a mutant of the nuclear receptor RORalpha. Circulation 98(24):2738-43PubMed: 9851961 MGI: J:52105

View All References

Genetics

a

Allele Symbol: a

Allele Name	nonagouti
Allele Type	Spontaneous
Allele Synonym(s)
Gene Symbol and Name	a, nonagouti
Gene Synonym(s)
Strain of Origin	old mutant of the mouse fancy
Chromosome	2
General Note	Insertion of the LV30 retrotransposon without the beta4 retrovirus sequence does not cause the nonagouti phenotype. J:278039
Molecular Note	Characterization of this allele shows an insertion of DNA comprised of a 5.5kb virus-like element, VL30, into the first intron of the agouti gene. The VL30 element itself contains an additional 5.5 kb sequence, flanked by 526 bp of direct repeats (beta4 retroviral sequence). The host integration site is the same as for a^t-2Gso and A^w-38J and includes a duplication of four nucleotides of host DNA and a deletion of 2 bp from the end of each repeat. Northern analysis of mRNA from skin of homozygotes shows a smaller agouti message and levels 8 fold lower than found in wild-type.

Rora^sg

Allele Symbol: Rora^sg

Allele Name	staggerer
Allele Type	Spontaneous
Allele Synonym(s)	RORalpha^-; sg
Gene Symbol and Name	Rora, RAR-related orphan receptor alpha
Gene Synonym(s)
Strain of Origin	obese stock
Chromosome	9
Molecular Note	This allele contains a 6.5kb genomic deletion of an exon encoding part of the ligand binding domain. The deletion results in an exon-skipping event that introduces a shift in the reading frame. The resulting protein is predicted to be truncated due to introduction of a premature stop codon.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Rora^sg related

Neurobiology Research
- Ataxia (Movement) Defects
- Receptor Defects
- Tremor Defects
- Cerebellar Defects
  - Purkinje cell defect

Mammalian Phenotype Terms by Genotype

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

Genotype: Rora^sg/Rora^sg
involves: obese stock

behavior/neurological phenotype

abnormal gait
- abnormal gait is apparent at ~2 weeks of age
- gait is shuffling and hesitant, interrupted every few steps by lurching motions side-to-side

impaired coordination
- mice fall off an elevated rod on average of 13 seconds compared to over 3 minutes for WT mice
- mice fall off an elevated rod on average of 13 seconds compared to over 3 minutes for WT mice

decreased grip strength
- mice have a mean hanging time of 12 seconds compared to over 3 minutes for WT mice

limb grasping
- is observed in all mice

abnormal motor learning
- mice hang onto the rod as opposed the walking strategy WT mice exclusively use
- mice have an impaired ability to learn how to hang onto a rotating rod
- scores do not improve with 10 days of training

ataxia
- treatment with a thyrotropin releasing hormone analog improves ataxia (fewer falls in a given distance travelled)

abnormal limb posture
- some animals have hindlimbs held abducted and everted at 45 degrees at rest

abnormal motor capabilities/coordination/movement

hypoactivity
- mutants remain stationary much more than littermates

tremors
- mild tremors accompany initiation of movement

growth/size/body region phenotype

decreased body size
- mutants are smaller than littermates

homeostasis/metabolism phenotype

abnormal hormone level
- prothyrotropin releasing hormone levels are elevated in the thalamus, cerebellum, brainstem, and spinal cord

mortality/aging

postnatal lethality, incomplete penetrance
- about 50% of mutants die by weaning

nervous system phenotype

abnormal cerebellar layer morphology

abnormal olfactory bulb glomerular layer morphology
- reduced number of interneuronal relays
- thinner than controls
- glomerular surface reduced about 15%
- reduced cell number and intercellular space

abnormal olfactory bulb internal plexiform layer morphology
- less distinct
- thinner than controls

small cerebellum
- less than half of control weight at 5 days of age
- weight is significantly less than controls even before neurological symptoms appear

abnormal olfactory bulb mitral cell layer morphology
- somewhat discontinuous

abnormal cerebellar foliation

abnormal cerebellar granule cell morphology
- conspicuous differences in the internal granule layer at 10 days of age
- external granule layer less developed at birth
- reduced rate of cell proliferation at 1 and 5 days of age
- cells migrate prematurely from the external granule layer having undergone fewer cell divisions

abnormal cerebellar molecular layer

abnormal cochlear VIII nucleus morphology
- cochlear nuclei are reduced in volume and severely malformed
- dendritic spines are rare on cartwheel cells at 1 month of age
- cartwheel cells are rarely seen in adults

abnormal olfactory bulb granule cell morphology
- pycnotic nuclei
- vacuolations and ruptured membranes

abnormal olfactory bulb outer nerve layer morphology
- glial cells with more processes ensheathing axons in the nerve layer

abnormal cerebellum morphology
- adult cerebellar cell surface with embryonic characteristics
- cerebellum is less than one-third the size of wild-type littermates
- cerebellum of adults shows tiny folia with indistinct fissures
- cells agglutinable with wheat germ agglutinin but not wit h Con-A

abnormal olfactory bulb external plexiform layer morphology
- thinner than controls
- large, empty, intercellular spaces
- lower density of secondary dendrites

thin cerebellar molecular layer

abnormal brain morphology

abnormal nervous system physiology
- immunoreactive somatostatin is significantly elevated in both the cerebrum and in the cerebellum

abnormal olfactory bulb granule cell layer morphology
- composed of several layers of anaxonal interneurons with smaller than normal cell bodies
- nuclear size is smaller than controls

abnormal olfactory bulb layer morphology

abnormal olfactory bulb morphology
- dendro-dendritic asymmetrical synapses are abundant
- fewer astrocytes found

abnormal cerebellar granule layer morphology
- granular cell layer displays a paucity of cells in mutants

abnormal Purkinje cell morphology
- cells are randomly oriented
- poorly elaborated dendritic trees

decreased cerebellar granule cell number
- 25% reduction in granule cells in the internal granule cell layer

small olfactory bulb
- volume slightly reduced

Genotype: Rora^sg/Rora^sg
involves: C57BL/6

behavior/neurological phenotype

abnormal maternal nurturing
- females from heterozygous parents fail to nurture pups to weaning
- females from selected homozygous lineages sometimes (9/14) raise pups to weaning although growth rate of pups is lower than normal

abnormal spatial learning
- higher latency to escape at all time tested using two types of water maze
- less age related degradation in latency to escape although it is always greater than in controls

abnormal sexual interaction
- one to two months of social isolation results in increased mounting behavior when a receptive female is encountered
- successful mating occurs from 35-160 days after the end of male isolation
- vestibular stimulation improves the ability of males to mate with experienced females

cardiovascular system phenotype

atherosclerotic lesions
- the atherosclerotic lesions induced in homozygotes by 9 weeks of an atherosclerotic diet have a 6 fold greater area in female homozygotes and a 7.5 fold greater area in male homozygotes than those in wild-type controls on the same diet

decreased mean systemic arterial blood pressure
- phenylephrine causes less blood pressure increase than in controls
- 80mmHg vs 87mmHg for controls
- acetyl choline causes less blood pressure decrease than in controls

increased angiogenesis
- 80% rise in vascular density relative to controls
- 3 fold increase in capillary density relative to controls
- significantly increased in the ischemic leg 28 days after femoral artery ligature

abnormal vasoconstriction
- contractions of the mesenteric artery induced by phenylephrin or serotonin are less than in controls

abnormal vasodilation
- endothelium-dependent and independent dilation is reduced
- blood flow induced dilation of the mesenteric artery is less than for controls

increased susceptibility to atherosclerosis
- Although homozygotes fed a normal diet do not display abnormal atherosclerotic lesions, 9 weeks of an atherosclerotic diet induces exaggerated altherosclerotic lesions compared with wild-type controls on the atherosclerotic diet

endocrine/exocrine gland phenotype

thymus atrophy

hematopoietic system phenotype

increased IgE level
- levels are elevated in unsensitized mice
- OVA sensitization causes an additional elevation in IgE levels
- OVA challenge of sensitized mice causes a very great increase in IgE levels

spleen atrophy

abnormal macrophage physiology
- LPS stimulated macrophage produce 2 fold more IL-1 relative to macrophage of controls

thymus atrophy

homeostasis/metabolism phenotype

abnormal lipid homeostasis
- plasma APOA1 and APOA2 concentrations are approximately 2 fold lower than in wild-type controls on a normal diet, and the Apoa1 mRNA level in intestine is diminished relative to wild-type, although liver expression of Apoa1 is comparable with wild-type
- the production rate of APOA1 is diminished, but the fractional catabolic rate is comparable to wild-type

decreased circulating HDL cholesterol level
- therogenic diet.
- plasma HDL cholesterol level is significantly lower in both male and female homozygotes than in wild-type controls, and females have significantly lower plasma HDL level than males both for the homozygous and wild-type data sets. This is true even on an atherogenic diet.

decreased circulating cholesterol level
- although cholesterol levels increase on an atherosclerotic diet, homozygotes still have lower plasma cholesterol than wild-type controls also fed this diet
- plasma total cholesterol levels are significantly lower in both male and female homozygotes than in wild-type controls

immune system phenotype

increased IgE level
- OVA challenge of sensitized mice causes a very great increase in IgE levels
- levels are elevated in unsensitized mice
- OVA sensitization causes an additional elevation in IgE levels

increased interleukin-1 secretion
- LPS stimulated macrophage produce 2 fold more IL-1 relative to macrophage of controls

lung inflammation
- less alveolar infiltration as well
- less increase of IL-4, IL-5, and IL-13
- OVA sensitized and challenged mice experience less infiltration of lymphocytes and polymorphonuclear cells into peribronchiolar and perivascular regions of the lungs
- less increase of inflammatory cells in bronchoalveolar lavage

abnormal immune system physiology
- abnormal immune responses

abnormal immune system organ morphology

abnormal macrophage physiology
- LPS stimulated macrophage produce 2 fold more IL-1 relative to macrophage of controls

spleen atrophy

thymus atrophy

mammalian phenotype

taste/olfaction phenotype
- Normal - male mice are able to distinguish between the vaginal secretions of estrus and non-estrus females

immune system phenotype
- white blood cell, lymphocyte, and neutrophil counts are not significantly different between homozygotes and wild-type controls

muscle phenotype

abnormal vasodilation
- endothelium-dependent and independent dilation is reduced
- blood flow induced dilation of the mesenteric artery is less than for controls

abnormal vasoconstriction
- contractions of the mesenteric artery induced by phenylephrin or serotonin are less than in controls

nervous system phenotype

abnormal inferior olivary complex morphology
- decreased cell density
- definition of subnuclei is better in 21 day old mice but regresses in adults
- number of neurons drops 30% within 3 days of birth and continues to decline for 2 months
- number of neurons in adults is decreased 60% relative to newborns
- individual olivary subnuclei are poorly defined relative to controls
- inferior olive extends further dorsally in the midline
- adult cell bodies are smaller than in newborns
- olivary dendrites tend to be multipolar and well branched

abnormal cerebellum morphology
- embryonic, high sialic acid forms of N-CAM persist on cell surfaces to 14 and 21 days of age

reproductive system phenotype

prolonged estrus
- prolonged vaginal estrus relative to controls

abnormal estrous cycle
- irregular cycles

abnormal external female genitalia morphology
- vaginal opening averaged 35 days (never earlier than 31 days) while controls averaged 28 days (earliest 26 days)

prolonged metestrus

delayed estrous cycle
- onset of estrus at 45 days vs 40 days for controls

reduced female fertility
- no females mate before 2.5 months of age
- only one of 10 females still mating at 6 months of age
- females sexual activity decreases after 4.5 months

abnormal female reproductive system physiology

abnormal fertility/fecundity
- no unstimulated couples mated
- some couples receiving vestibular stimulation mated between the ages of 36 and 89 days of age

respiratory system phenotype

lung inflammation
- OVA sensitized and challenged mice experience less infiltration of lymphocytes and polymorphonuclear cells into peribronchiolar and perivascular regions of the lungs
- less alveolar infiltration as well
- less increase of inflammatory cells in bronchoalveolar lavage
- less increase of IL-4, IL-5, and IL-13

abnormal respiratory mucosa morphology
- less mucous cell hyperplasia in airways after OVA exposure of sensitized mice

abnormal lung compliance
- lung resistance in response to methacholine challenge of OVA exposed mice fails to increase

taste/olfaction phenotype

abnormal olfaction
- N1 and N2 response amplitudes of the evoked field potential are significantly reduced
- attractive threshold concentration for vanillin is increased
- amyl alchohol odor induced evoked field potential shows an increased latency preceding the functional response of mitral cells in the olfactory bulb
- aversive threshold concentration for butanol is increased

Genotype: Rora^sg/Rora^sg
involves: C57BL

cellular phenotype

abnormal Purkinje cell differentiation
- retarded

nervous system phenotype

abnormal cerebellar granule layer morphology

abnormal cerebellar Purkinje cell layer
- Purkinje cell band thicker at 3 days of age

abnormal Purkinje cell morphology
- multiple climbing fiber synaptic connections to each Purkinje cell are maintained
- 60-90% of Purkinje cells are lost
- cells smaller in size with thinner processes
- larger, typical Purkinje cells are absent in intermediate regions of the cerebellum

increased noradrenaline level
- significantly elevated in cerebral cortex
- measurably increased in the spinal cord
- significantly elevated in cerebellum

thin cerebellar granule layer

thin cerebellar molecular layer

abnormal cerebellar layer morphology

abnormal cerebellum morphology
- cell surface antigen characteristics more embryonic in nature

abnormal synaptic glutamate release
- levels continue to drop over time
- glutamate levels drop between 7 and 10 days

abnormal cerebellum deep nucleus morphology
- area occupied by deep neurons is reduced to 36% of controls but cell numbers are not reduced
- white matter in deep cerebellar nuclei is reduced to 42% of controls
- neurons in the deep nuclei are smaller than seen in controls

abnormal Purkinje cell dendrite morphology
- no synapses form between Purkinje cell spines and the parallel fibers at 14 to 43 days of age
- reduced growth of dendrite arbor

abnormal cerebellar granule cell morphology
- degenerating parallel fibers begin to appear around 7 days and is well advanced by 14 days
- no synapses form between the parallel fibers and the Purkinje cell spines at 14 to 43 days of age
- synapses do develop between parallel fibers and stellate and basket cells

abnormal Purkinje cell differentiation
- retarded

decreased aspartic acid level
- aspartate levels decline between 7 and 10 days; low levels persist

decreased gamma-aminobutyric acid level
- GABA levels in deep cerebellar nuclei are reduced at all ages examined
- GABA levels are 52% of controls at 7 days and 30% at 3 weeks

delaminated Purkinje cell layer
- typical laminar array fails to form

small cerebellum
- 62% of normal weight at birth
- weight is 36% of normal at 7 days

homeostasis/metabolism phenotype

decreased taurine level
- taurine levels decline between 7 and 10 days; low levels persist

decreased gamma-aminobutyric acid level
- GABA levels in deep cerebellar nuclei are reduced at all ages examined
- GABA levels are 52% of controls at 7 days and 30% at 3 weeks

increased noradrenaline level
- significantly elevated in cerebellum
- measurably increased in the spinal cord
- significantly elevated in cerebral cortex

decreased aspartic acid level
- aspartate levels decline between 7 and 10 days; low levels persist

Genotype: Rora^sg/Rora⁺
involves: C57BL/6J

behavior/neurological phenotype

abnormal spatial learning
- mice exhibit impaired spatial learning in a Z-maze filled with water compared with wild-type mice

Genotype: Rora^sg/Rora⁺
involves: C57BL

nervous system phenotype

abnormal cerebellar layer morphology

abnormal cerebellum morphology

abnormal inferior olivary complex morphology
- neuron counts are 60% of controls at 1 year of age

decreased Purkinje cell number
- significant loss of Purkinje cells at 1 year of age

abnormal cerebellar granule layer morphology
- granule cell layer decreases with age
- cell density is reduced

decreased cerebellar granule cell number
- cell numbers are about 35% of controls

small cerebellum
- decreased cross-sectional area of the cerebellum at 1 year of age

References

Mamontova A; Seguret-Mace S; Esposito B; Chaniale C; Bouly M; Delhaye-Bouchaud N; Luc G; Staels B; Duverger N; Mariani J; Tedgui A. 1998. Severe atherosclerosis and hypoalphalipoproteinemia in the staggerer mouse, a mutant of the nuclear receptor RORalpha. Circulation 98(24):2738-43PubMed: 9851961 MGI: J:52105

Additional References

Kopmels B; Wollman EE; Guastavino JM; Delhaye-Bouchaud N; Fradelizi D; Mariani J. 1990. Interleukin-1 hyperproduction by in vitro activated peripheral macrophages from cerebellar mutant mice. J Neurochem 55(6):1980-5PubMed: 2230805 MGI: J:28095
Yoon CH. 1972. Developmental mechanism for changes in cerebellum of staggerer mouse, a neurological mutant of genetic origin. Neurology 22(7):743-54PubMed: 4673255 MGI: J:5304

Additional - a related

Additional - Rora^sg related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Rora
- Standard PCR:Rora
- Genotyping resources and troubleshooting
Appearance
- black, ataxic, tremors
  Related Genotype: a/a Rora^sg/Rora^sg
  
  black, unaffected
  Related Genotype: a/a +/? or a/a Rora^sg/+
Citation
When using the staggerer mouse strain in a publication, please cite the originating article(s) and include JAX stock #000237 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

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> >	Homozygous for a, Heterozygous or wildtype for Rora<sg>

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Frozen Mouse Embryo	B6C3Fe a/a-Rora<sg>/J Frozen Embryos	$2595.00
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Frozen Mouse Embryo	B6C3Fe a/a-Rora<sg>/J Frozen Embryos	$3373.50
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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Also Known As:staggerer

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

a

Allele Symbol: a

Rorasg

Allele Symbol: Rorasg

Disease Terms

Research Areas By Phenotype

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

Genotype: Rorasg related

Mammalian Phenotype Terms by Genotype

Genotype: Rorasg/Rorasginvolves: obese stock

behavior/neurological phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

mortality/aging

nervous system phenotype

Genotype: Rorasg/Rorasginvolves: C57BL/6

behavior/neurological phenotype

cardiovascular system phenotype

endocrine/exocrine gland phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

mammalian phenotype

muscle phenotype

nervous system phenotype

reproductive system phenotype

respiratory system phenotype

taste/olfaction phenotype

Genotype: Rorasg/Rorasginvolves: C57BL

cellular phenotype

nervous system phenotype

homeostasis/metabolism phenotype

Genotype: Rorasg/Rora+involves: C57BL/6J

behavior/neurological phenotype

Genotype: Rorasg/Rora+involves: C57BL

nervous system phenotype

References

Additional References

Additional - a related

Additional - Rorasg related

Genotyping Protocols

Appearance

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Rora^sg

Allele Symbol: Rora^sg

Genotype: Rora^sg related

Genotype: Rora^sg/Rora^sg
involves: obese stock

Genotype: Rora^sg/Rora^sg
involves: C57BL/6

Genotype: Rora^sg/Rora^sg
involves: C57BL

Genotype: Rora^sg/Rora⁺
involves: C57BL/6J

Genotype: Rora^sg/Rora⁺
involves: C57BL

Additional - Rora^sg related