Phenotypes associated with this allele

• Allele Symbol: Rora^sg
• Allele Name: staggerer
• Allele ID: MGI:1857035
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Rora^sg/Rora^sg	involves: C57BL	MGI:4835188
hm2	Rora^sg/Rora^sg	involves: C57BL/6	MGI:3720640
hm3	Rora^sg/Rora^sg	involves: obese stock	MGI:2174717
ht4	Rora^sg/Rora^+	involves: C57BL	MGI:4835189
ht5	Rora^sg/Rora^+	involves: C57BL/6J	MGI:4820957

Genotype
MGI:4835188

hm1

• Allelic Composition: Rora^sg/Rora^sg
• Genetic Background: involves: C57BL

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

nervous system

abnormal cerebellum morphology ( J:6088 )

• cell surface antigen characteristics more embryonic in nature

abnormal cerebellar layer morphology ( J:5968 )

abnormal cerebellar Purkinje cell layer ( J:5968 )

• Purkinje cell band thicker at 3 days of age

abnormal Purkinje cell morphology ( J:6185 , J:6260 )

• larger, typical Purkinje cells are absent in intermediate regions of the cerebellum (J:6185)

• 60-90% of Purkinje cells are lost (J:6185)

• multiple climbing fiber synaptic connections to each Purkinje cell are maintained (J:6260)

abnormal Purkinje cell differentiation ( J:5968 )

• retarded

abnormal Purkinje cell dendrite morphology ( J:5968 )

• no synapses form between Purkinje cell spines and the parallel fibers at 14 to 43 days of age

• reduced growth of dendrite arbor

decreased Purkinje cell size ( J:5968 )

• cells smaller in size with thinner processes

delaminated Purkinje cell layer ( J:5968 )

• typical laminar array fails to form

abnormal cerebellar granule layer morphology ( J:5968 )

abnormal cerebellar granule cell morphology ( J:5968 )

• 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

• degenerating parallel fibers begin to appear around 7 days and is well advanced by 14 days

thin cerebellar granule layer ( J:5968 )

thin cerebellar molecular layer ( J:5968 )

abnormal cerebellum deep nucleus morphology ( J:6554 )

• white matter in deep cerebellar nuclei is reduced to 42% of controls

• area occupied by deep neurons is reduced to 36% of controls but cell numbers are not reduced

• neurons in the deep nuclei are smaller than seen in controls

small cerebellum ( J:6875 )

• 62% of normal weight at birth

• weight is 36% of normal at 7 days

abnormal synaptic glutamate release ( J:6875 )

• glutamate levels drop between 7 and 10 days

• levels continue to drop over time

homeostasis/metabolism

decreased aspartic acid level ( J:6875 )

• aspartate levels decline between 7 and 10 days; low levels persist

decreased gamma-aminobutyric acid level ( J:6875 )

• 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

decreased taurine level ( J:6875 )

• taurine levels decline between 7 and 10 days; low levels persist

increased noradrenaline level ( J:164122 )

• significantly elevated in cerebellum

• significantly elevated in cerebral cortex

• measurably increased in the spinal cord

cellular

abnormal Purkinje cell differentiation ( J:5968 )

• retarded

Genotype
MGI:3720640

hm2

• Allelic Composition: Rora^sg/Rora^sg
• Genetic Background: involves: C57BL/6

homeostasis/metabolism

abnormal lipid homeostasis ( J:52105 )

• 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 cholesterol level ( J:52105 )

• plasma total cholesterol levels are significantly lower in both male and female homozygotes than in wild-type controls

• although cholesterol levels increase on an atherosclerotic diet, homozygotes still have lower plasma cholesterol than wild-type controls also fed this diet

decreased circulating HDL cholesterol level ( J:52105 )

• 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.

cardiovascular system

atherosclerotic lesions ( J:52105 )

• 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

increased susceptibility to atherosclerosis ( J:52105 )

• 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

increased angiogenesis ( J:115425 )

• significantly increased in the ischemic leg 28 days after femoral artery ligature

• 80% rise in vascular density relative to controls

• 3 fold increase in capillary density relative to controls

decreased mean systemic arterial blood pressure ( J:109735 )

• 80mmHg vs 87mmHg for controls

• phenylephrine causes less blood pressure increase than in controls

• acetyl choline causes less blood pressure decrease than in controls

abnormal vasoconstriction ( J:109735 )

• contractions of the mesenteric artery induced by phenylephrin or serotonin are less than in controls

abnormal vasodilation ( J:109735 )

• blood flow induced dilation of the mesenteric artery is less than for controls

• endothelium-dependent and independent dilation is reduced

immune system

immune system phenotype ( J:52105 )

N • white blood cell, lymphocyte, and neutrophil counts are not significantly different between homozygotes and wild-type controls

abnormal immune system organ morphology ( J:2228 )

thymus atrophy ( J:2228 )

spleen atrophy ( J:2228 )

abnormal immune system physiology ( J:2228 )

• abnormal immune responses

increased IgE level ( J:135863 )

• 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

abnormal macrophage physiology ( J:28095 )

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

increased interleukin-1 secretion ( J:28095 )

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

lung inflammation ( J:135863 )

• 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

nervous system

abnormal inferior olivary complex morphology ( J:20982 , J:28468 )

• individual olivary subnuclei are poorly defined relative to controls (J:20982)

• definition of subnuclei is better in 21 day old mice but regresses in adults (J:20982)

• olivary dendrites tend to be multipolar and well branched (J:20982)

• number of neurons drops 30% within 3 days of birth and continues to decline for 2 months (J:20982)

• number of neurons in adults is decreased 60% relative to newborns (J:20982)

• adult cell bodies are smaller than in newborns (J:20982)

• inferior olive extends further dorsally in the midline (J:28468)

• decreased cell density (J:28468)

abnormal cerebellum morphology ( J:6930 )

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

reproductive system

abnormal external female genitalia morphology ( J:1960 )

♀ • vaginal opening averaged 35 days (never earlier than 31 days) while controls averaged 28 days (earliest 26 days)

abnormal female reproductive system physiology ( J:1960 )

♀

abnormal estrous cycle ( J:1960 )

♀ • irregular cycles

delayed estrous cycle ( J:1960 )

♀ • onset of estrus at 45 days vs 40 days for controls

prolonged estrus ( J:1960 )

♀ • prolonged vaginal estrus relative to controls

prolonged metestrus ( J:1960 )

♀

abnormal fertility/fecundity ( J:14535 )

• some couples receiving vestibular stimulation mated between the ages of 36 and 89 days of age

• no unstimulated couples mated

reduced female fertility ( J:1960 )

♀ • no females mate before 2.5 months of age

♀ • females sexual activity decreases after 4.5 months

♀ • only one of 10 females still mating at 6 months of age

behavior/neurological

abnormal spatial learning ( J:30012 )

• 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 maternal nurturing ( J:14497 )

♀ • 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 sexual interaction ( J:14535 , J:26698 )

♂ • vestibular stimulation improves the ability of males to mate with experienced females (J:14535)

♂ • one to two months of social isolation results in increased mounting behavior when a receptive female is encountered (J:26698)

♂ • successful mating occurs from 35-160 days after the end of male isolation (J:26698)

respiratory system

lung inflammation ( J:135863 )

• 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 ( J:135863 )

• less mucous cell hyperplasia in airways after OVA exposure of sensitized mice

abnormal lung compliance ( J:135863 )

• lung resistance in response to methacholine challenge of OVA exposed mice fails to increase

taste/olfaction

taste/olfaction phenotype ( J:15645 )

N • male mice are able to distinguish between the vaginal secretions of estrus and non-estrus females

abnormal olfaction ( J:39053 , J:107925 )

• aversive threshold concentration for butanol is increased (J:39053)

• attractive threshold concentration for vanillin is increased (J:39053)

• amyl alchohol odor induced evoked field potential shows an increased latency preceding the functional response of mitral cells in the olfactory bulb (J:107925)

• N1 and N2 response amplitudes of the evoked field potential are significantly reduced (J:107925)

hematopoietic system

thymus atrophy ( J:2228 )

spleen atrophy ( J:2228 )

increased IgE level ( J:135863 )

• 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

abnormal macrophage physiology ( J:28095 )

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

muscle

abnormal vasoconstriction ( J:109735 )

• contractions of the mesenteric artery induced by phenylephrin or serotonin are less than in controls

abnormal vasodilation ( J:109735 )

• blood flow induced dilation of the mesenteric artery is less than for controls

• endothelium-dependent and independent dilation is reduced

endocrine/exocrine glands

thymus atrophy ( J:2228 )

Genotype
MGI:2174717

hm3

• Allelic Composition: Rora^sg/Rora^sg
• Genetic Background: involves: obese stock

mortality/aging

postnatal lethality, incomplete penetrance ( J:13140 )

• about 50% of mutants die by weaning

nervous system

abnormal brain morphology ( J:13140 )

abnormal cochlear VIII nucleus morphology ( J:121314 )

• 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 morphology ( J:55239 )

• fewer astrocytes found

• dendro-dendritic asymmetrical synapses are abundant

abnormal olfactory bulb layer morphology ( J:55239 )

abnormal olfactory bulb external plexiform layer morphology ( J:55239 )

• thinner than controls

• lower density of secondary dendrites

• large, empty, intercellular spaces

abnormal olfactory bulb glomerular layer morphology ( J:55239 )

• thinner than controls

• glomerular surface reduced about 15%

• reduced cell number and intercellular space

• reduced number of interneuronal relays

abnormal olfactory bulb granule cell layer morphology ( J:55239 )

• composed of several layers of anaxonal interneurons with smaller than normal cell bodies

• nuclear size is smaller than controls

abnormal olfactory bulb granule cell morphology ( J:55239 )

• pycnotic nuclei

• vacuolations and ruptured membranes

abnormal olfactory bulb internal plexiform layer morphology ( J:55239 )

• thinner than controls

• less distinct

abnormal olfactory bulb mitral cell layer morphology ( J:55239 )

• somewhat discontinuous

abnormal olfactory bulb outer nerve layer morphology ( J:55239 )

• glial cells with more processes ensheathing axons in the nerve layer

small olfactory bulb ( J:55239 )

• volume slightly reduced

abnormal cerebellum morphology ( J:6068 , J:13140 )

• adult cerebellar cell surface with embryonic characteristics (J:6068)

• cells agglutinable with wheat germ agglutinin but not wit h Con-A (J:6068)

• cerebellum of adults shows tiny folia with indistinct fissures (J:13140)

• cerebellum is less than one-third the size of wild-type littermates (J:13140)

abnormal cerebellar foliation ( J:13140 )

abnormal cerebellar layer morphology ( J:5304 )

abnormal Purkinje cell morphology ( J:121314 )

• cells are randomly oriented

• poorly elaborated dendritic trees

abnormal cerebellar granule layer morphology ( J:13140 )

• granular cell layer displays a paucity of cells in mutants

abnormal cerebellar granule cell morphology ( J:5304 )

• 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

• conspicuous differences in the internal granule layer at 10 days of age

decreased cerebellar granule cell number ( J:5304 )

• 25% reduction in granule cells in the internal granule cell layer

abnormal cerebellar molecular layer ( J:13140 )

thin cerebellar molecular layer ( J:13140 )

small cerebellum ( J:5304 , J:13140 )

• weight is significantly less than controls even before neurological symptoms appear (J:5304)

• less than half of control weight at 5 days of age (J:5304)

abnormal nervous system physiology ( J:28478 )

• immunoreactive somatostatin is significantly elevated in both the cerebrum and in the cerebellum

behavior/neurological

abnormal motor learning ( J:46854 )

• mice have an impaired ability to learn how to hang onto a rotating rod

• mice hang onto the rod as opposed the walking strategy WT mice exclusively use

• scores do not improve with 10 days of training

abnormal motor capabilities/coordination/movement ( J:13140 )

limb grasping ( J:46854 )

• is observed in all mice

tremors ( J:13140 )

• mild tremors accompany initiation of movement

ataxia ( J:13140 , J:18435 )

• treatment with a thyrotropin releasing hormone analog improves ataxia (fewer falls in a given distance travelled) (J:18435)

impaired coordination ( J:13140 , J:46854 )

• mice fall off an elevated rod on average of 13 seconds compared to over 3 minutes for WT mice (J:46854)

decreased grip strength ( J:46854 )

• mice have a mean hanging time of 12 seconds compared to over 3 minutes for WT mice

abnormal limb posture ( J:13140 )

• some animals have hindlimbs held abducted and everted at 45 degrees at rest

abnormal gait ( J:13140 )

• gait is shuffling and hesitant, interrupted every few steps by lurching motions side-to-side

• abnormal gait is apparent at ~2 weeks of age

decreased locomotor activity ( J:13140 )

• mutants remain stationary much more than littermates

growth/size/body

decreased body size ( J:13140 )

• mutants are smaller than littermates

homeostasis/metabolism

abnormal hormone level ( J:28467 )

• prothyrotropin releasing hormone levels are elevated in the thalamus, cerebellum, brainstem, and spinal cord

Genotype
MGI:4835189

ht4

• Allelic Composition: Rora^sg/Rora⁺
• Genetic Background: involves: C57BL

nervous system

abnormal inferior olivary complex morphology ( J:1431 )

• neuron counts are 60% of controls at 1 year of age

abnormal cerebellum morphology ( J:1431 )

abnormal cerebellar layer morphology ( J:1431 )

decreased Purkinje cell number ( J:1431 )

• significant loss of Purkinje cells at 1 year of age

abnormal cerebellar granule layer morphology ( J:1431 )

• granule cell layer decreases with age

• cell density is reduced

decreased cerebellar granule cell number ( J:1431 )

• cell numbers are about 35% of controls

small cerebellum ( J:1431 )

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

Genotype
MGI:4820957

ht5

• Allelic Composition: Rora^sg/Rora⁺
• Genetic Background: involves: C57BL/6J

behavior/neurological

abnormal spatial learning ( J:30686 )

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