Phenotypes Associated with This Genotype

Genotype
MGI:5757135

• Allelic Composition: Frrs1l^{tm1b(EUCOMM)Hmgu}/Frrs1l^{tm1b(EUCOMM)Hmgu}
• Genetic Background: C57BL/6N-Frrs1l^{tm1b(EUCOMM)Hmgu}/H
• Cell Lines: HEPD0701_4_B11

Data Sources

IMPC Data for Frrs1l

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

behavior/neurological

impaired cued conditioning behavior ( J:272893 )

♂ • mice exhibit deficits in cued, but not contextual, fear conditioning, indicating an inability to learn the association between a tone and an aversive stimulus and impaired implicit memory

impaired spatial working memory ( J:272893 )

♀ • mice show no preference for the novel arm in the Y-maze forced alternation test, suggesting a working memory deficit

limb grasping ( J:211773 , J:272893 )

♀ • mice exhibit reduced muscle force associated with an increased incidence of limb grasping at 3, 6, and 9 months of age (J:272893)

IMPC - HAR ♂ (J:211773)

impaired coordination ( J:272893 )

♀ • mice exhibit a shorter latency to fall on the accelerating rotarod

♀ • in wheel-running, mice show no differences are seen from wild-type mice in the first two weeks but when the standard wheel is replaced by a complex wheel that introduces a new challenge at the third week, mice are unable to run at all, showing a drop in running attempts to almost zero

decreased grip strength ( J:211773 , J:272893 )

♀ • 9-month-old mice show a loss of grip when climbing down a vertical grip (J:272893)

♀ • grip force in all 4 limbs is reduced at 3, 6, and 9 months; the loss of ability to grip is seen from an early age without further deterioration, suggesting a developmental non-progressive phenotype (J:272893)

IMPC - HAR ♂ (J:211773)

trunk curl ( J:211773 )

♂

IMPC - HAR

abnormal locomotor behavior ( J:211773 )

IMPC - HAR

impaired limb coordination ( J:272893 )

♀ • 9-month-old mice show a lack coordination as demonstrated by inability to place feet correctly on a grid floor

abnormal gait ( J:211773 , J:272893 )

IMPC - HAR (J:211773)

♀ • mice have an abnormal gait which is evident at weaning (J:272893)

♀ • in the horizontal ladder challenge (locotronic), mice show increased frequency of errors (misplacement of feet) while moving along the horizontal ladder (J:272893)

hyperactivity ( J:211773 , J:272893 )

IMPC - HAR ♀ (J:211773)

MGI

♀ • mice exhibit increased activity in the home cage at 10 weeks of age throughout both light and dark phases and increased activity at 6 and 9 months in the dark phase only (J:272893)

♀ • in the novel environment of the open-field, mice exhibit increased activity, with greater total distance moved and increased velocity (J:272893)

♀ • frequency to enter the center of the arena and velocity in the center of the arena are also increased, however the distance moved and duration in the center are not different, indicating hyperactivity (J:272893)

increased stereotypic behavior ( J:272893 )

♀ • 2 of 9 females exhibit self-inflicted wounds and stereotypical behavior

decreased sleep duration ( J:272893 )

♀ • total immobility-defined sleep is less than in controls in the dark phase of the light/dark cycle

fragmentation of sleep/wake states ( J:272893 )

♀ • mice have a fragmented sleep pattern, with less time asleep overall and shorter sleep bouts in the dark phase of the light/dark cycle

♀ • however, mice show no overt changes in circadian period or entrainment

seizures ( J:272893 )

• some mice exhibit behavioral seizures, consisting of episodes of behavioral arrest and lordotic postures and one mouse died during a generalized convulsion

growth/size/body

decreased body size ( J:272893 )

• shorter tibia length and therefore smaller body size

decreased body weight ( J:272893 )

• all mice that survive to weaning show prominent reduced body weight from 6 months onward

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:272893 )

♀N • no differences in body composition or calorimetric measurements of metabolic rate

integument

absent vibrissae ( J:211773 )

♂

IMPC - HAR

mortality/aging

preweaning lethality, incomplete penetrance ( J:211773 )

IMPC - HAR

neonatal lethality, incomplete penetrance ( J:272893 )

• more than 90% of neonates die between 12 hours and 24 hours after birth

• however, mice are born at the expected Mendelian ratios and mice that survive past P2 continue to thrive to weaning and beyond

nervous system

seizures ( J:272893 )

• some mice exhibit behavioral seizures, consisting of episodes of behavioral arrest and lordotic postures and one mouse died during a generalized convulsion

abnormal brain morphology ( J:272893 )

• decrease in AMP receptor protein levels and in proportion of immature AMPA receptors in the brain

• however, synaptic numbers and levels of synaptic markers are unchanged

abnormal brain wave pattern ( J:272893 )

♂ • electroencephalographic (EEG) shows abnormalities with repeated runs of polyspikes and a seizure-like episode although discrete electrographic seizures are not seen indicating encephalopathy

decreased prepulse inhibition ( J:211773 )

IMPC - HAR

respiratory system

abnormal breathing pattern ( J:272893 )

♀ • 1 of 9 females exhibit breathing difficulties

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
developmental and epileptic encephalopathy 37		DOID:0080435	OMIM:616981	J:272893