Phenotypes Associated with This Genotype

Genotype
MGI:3695037

• Allelic Composition: Glrb^spa/Glrb^spa
• Genetic Background: Not Specified

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:13079 )

• percentage of mortality is high before or around weaning, although some can live almost a normal life span

muscle

muscle spasm ( J:5196 , J:13079 )

• suffer from periods of spasticity which vary in length from one to several minutes; they walk in short steps, on tip-toe and arch their backs (J:5196)

• spasticity is induced by sudden handling (J:5196)

• sudden disturbance or handling causes spasms in which the back is stiff and arched, the legs are stiff and stretched, and the toes are extended (J:13079)

• when held by their tails, backs become stiff and bodies and legs quiver with a high frequency of vibration (J:13079)

• mutants are recognizeable by 14 days of age (J:13079)

behavior/neurological

impaired righting response ( J:13079 )

• during a spasm, have great difficulty in turning over after being laid on the table with the belly facing upward

hyperekplexia ( J:33924 )

increased startle reflex ( J:33924 )

• exhibit increased startle responses to acoustic stimuli of different intensities

tremors ( J:5196 )

• when lifted up by the tail, backs stiffen and the entire body and legs quiver violently, indicating tremor

impaired swimming ( J:13079 )

• lack facility in swimming

abnormal posture ( J:13079 )

• in severe cases of spasms, mutants are arch-backed and slide on the table

abnormal gait ( J:13079 )

• walk on tip-toe during a stimulus-induced spasm

short stride length ( J:13079 )

• walk in short steps during a stimulus-induced spasm

abnormal maternal nurturing ( J:13079 )

♀ • females produce young but are poor mothers, possibly because of physical difficulties

reproductive system

reduced male fertility ( J:13079 )

♂ • frequency of litters from abnormal males is much lower

skeleton

abnormal vertebral column morphology ( J:5196 )

• vertebral column abnormalities, with the lumbar region most severely affected, that include intervertebral enchondrosis, hyperplasia of fibrocartilage, and intervertebral arthrosis, probably resulting from disc herniations and ossification

• as early as 24 days of age, exhibit formation of leptomeningeal cysts in the vertebral column, usually located medial to spinal nerve roots

• cysts are lined with a single or multiple layer of cuboidal epithelium and filled with a mucoid fluid and cellular debris and are located between the dura and the spinal cord

• the dorsal longitudinal ligament is thinner dorsally than medially

• in older mutants, the mucoid material ossifies and adheres to the spinal meninges

abnormal intervertebral disk morphology ( J:5196 )

• acute or subacute disc herniations; rupture of the annulus fibrosus leading to extrusion of the nucleus pulposus

• herniations of the nucleus pulposus are always dorsal or dorsolateral rather than medially

fragile skeleton ( J:5196 )

• skeleton becomes brittle with increasing age

nervous system

abnormal Purkinje cell morphology ( J:5196 )

• occasionally Purkinje cells are lost

abnormal brain dura mater morphology ( J:5196 )

• as cysts become distended with fluid, the dura is displaced laterally against the wall of the vertebral canal

abnormal dorsal root ganglion morphology ( J:5196 )

• necrobiotic changes involve the neurons of the spinal ganglia with certain of these calcifying and many have eccentric nuclei

abnormal spinal nerve morphology ( J:5196 )

• compression of the spinal roots by leptomeningeal cysts, leading to impingment of spinal root axons

• nerve fiber myelin and axonal changes occur in spinal roots, spinal nerves, cauda equina, and sciatic nerves

abnormal spinal cord morphology ( J:5196 )

• disc protrusions indent the ventral aspects of the spinal cord; indentations are often deep enough to alter the normal shape and symmetry of the spinal cord both in the white and grey matter

• white matter atrophies at the sites of compression

abnormal spinal cord ventral horn morphology ( J:5196 )

• ventral horn neurons become flattened or stretched due to the compression of the spinal cord and undergo degenerative changes, such as shrinkage, vacuolation, and necrobiosis

cardiovascular system

hemorrhage ( J:5196 )

• disk herniations cause hemorrhage

endocrine/exocrine glands

abnormal adrenal cortex morphology ( J:5196 )

• adrenal corticism is more evident in older mutants, beginning at about 2 months of age

enlarged adrenal glands ( J:5196 )

• enlarged due to cortical hypertrophy and hyperplasia

growth/size/body

decreased body size ( J:5196 )

homeostasis/metabolism

edema ( J:5196 )

• disc herniations cause edema

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hyperekplexia 2		DOID:0060697	OMIM:614619	J:33924