General Terms and Conditions

Related Disease (OMIM) Terms

	Jervell and Lange-Nielsen Syndrome; JLNS1
	Potassium Channel, Voltage-Gated, Isk-Related Subfamily, Member 1;

Mammalian Phenotype Terms assigned by genotype

Kcne1^tm1Sfh/Kcne1^tm1Sfh

        involves: 129S1/Sv

• behavior/neurological phenotype
• abnormal posture (MGI Ref ID J:105528)
  • homozygotes posture for an occipital rather than a forepaw landing when hung by the tail
  • however, at rest, the S-shaped, sagittal posture of the vertebral column is identical for wild type and mutant mice: both hold the head with the atlanto-occipital joint fully flexed, the cervico-thoracic junction fully flexed, and the cervical column upright
• abnormal vestibular response (MGI Ref ID J:105528)
  • as early as P7, homozygotes spontaneously roll on their backs more often than wild type mice, have difficuly righting themselves when placed on their backs, and are unable to swim
  • following unilateral labyrinthectomy, homozygotes fail to exhibit the expected oculomotor and postural changes (i.e. ocular nystagmus and static postural syndromes) observed in wild type mice
• circling (MGI Ref ID J:105528)
  • following unilateral labyrinthectomy, homozygotes continue to circle instead of exhibiting the expected static postural syndromes
  • unlike wild type mice, homozygotes cannot walk or run in a straight path in an open field or on a treadmill, and exhibit episodes of spontaneous circling during which the vertebral column maintains an S-shaped posture
• bi-directional circling (MGI Ref ID J:105528)
  • as mice mature, exhibit an intermittent bidirectional circling behavior
• unidirectional circling (MGI Ref ID J:105528)
  • interestingly, with time circling tends to become more unidirectional
• head bobbing (MGI Ref ID J:37461)
  • when at rest (i.e. alert but stationary), homozygotes show intermittent episodes of head bobbing with the head oscillating in the sagittal plane about the atlanto-occipital joint by 10-30° at 3-5 Hz
• head tilt (MGI Ref ID J:37461)
  • occasional head tilt
• absent pinna reflex (MGI Ref ID J:105528)
  • fail to show any pinnea reflex
• absent startle reflex (MGI Ref ID J:37461)
  • fail to show signs of startle
• absent vestibuloocular reflex (MGI Ref ID J:105528)
  • vestibulo-ocular reflex (VOR) testing indicates that head rotation fails to elicit compensatory slow-phase eye movements in mutant mice; no vestibular quick phases are generated at low frequencies
  • VOR gain is statistically insignificant at all frequencies and both velocities examined
• decreased startle reflex (MGI Ref ID J:105528)
• hyperactivity (MGI Ref ID J:37461)
• impaired coordination (MGI Ref ID J:37461)
  • when mutants begin to walk, exhibit an awkward uncoordinated movement
• impaired limb coordination (MGI Ref ID J:105528)
  • unlike wild type mice which perform a symmetrical gait at 0.5 m s^-1, with an equal time lag between the lay-down of the hindlimbs and forelimbs, homozygotes show episodes of circling and are incapable of following a linear trajectory
• impaired righting response (MGI Ref ID J:37461)
  • pups have difficulty righting themselves, however this disappears with maturation
  • as early as P7, homozygotes have difficuly righting themselves when placed on their backs
  • at P90, homozygotes show inhibition of righting when supine by cutaneous input to the feet
  • at P90, homozygotes land on their backs when dropped supine
• impaired swimming (MGI Ref ID J:37461)
  • mutants rotate along their long axis and sink
  • while underwater, mutants somersault while still rotating along their body length
  • as early as P7, homozygotes cannot swim
• stereotypic behavior (MGI Ref ID J:37461)
• circling (MGI Ref ID J:105528)
  • following unilateral labyrinthectomy, homozygotes continue to circle instead of exhibiting the expected static postural syndromes
  • unlike wild type mice, homozygotes cannot walk or run in a straight path in an open field or on a treadmill, and exhibit episodes of spontaneous circling during which the vertebral column maintains an S-shaped posture
• bi-directional circling (MGI Ref ID J:105528)
  • as mice mature, exhibit an intermittent bidirectional circling behavior
• unidirectional circling (MGI Ref ID J:105528)
  • interestingly, with time circling tends to become more unidirectional
• head bobbing (MGI Ref ID J:37461)
  • when at rest (i.e. alert but stationary), homozygotes show intermittent episodes of head bobbing with the head oscillating in the sagittal plane about the atlanto-occipital joint by 10-30° at 3-5 Hz
• hearing/vestibular/ear phenotype
• abnormal cochlea morphology (MGI Ref ID J:37461)
• abnormal cochlear sensory epithelium morphology (MGI Ref ID J:37461)
  • change in structure of the sensory epithelium is observed at P3
• cochlear hair cell degeneration (MGI Ref ID J:37461)
  • hair cells of the cochlear duct differentiate normally but degenerate postnatally, starting at around P3
• abnormal scala media morphology (MGI Ref ID J:37461)
• abnormal stria vascularis (MGI Ref ID J:37461)
  • exhibit an expansion of the intercellular space between marginal and intermediate cell processes, and between marginal cell processes and blood vessels
• absent organ of Corti (MGI Ref ID J:37461)
  • at P20, do not contain an organ of Corti
• cochlear hair cell degeneration (MGI Ref ID J:37461)
  • hair cells of the cochlear duct differentiate normally but degenerate postnatally, starting at around P3
• organ of Corti degeneration (MGI Ref ID J:37461)
  • seen at P3 in all turns of the cochlea, however degeneration of the supporting cells outside the organ of Corti does not occur until later (around P20)
• collapsed Reissner membrane (MGI Ref ID J:37461)
  • at P3, but not P0, Reissner's membrane is collapsed onto the surface of the spiral limbus, along the tectorial membrane and reticular lamina, and along the lateral wall of the clochlea in close opposition to the stria vascularis
• abnormal ear physiology (MGI Ref ID J:37461)
  • strial marginal cells and vestibular dark cells of the inner ear are unable to generate a short circuit current in vitro, indicating a lack of transepithelial potassium secretion
• abnormal vestibular response (MGI Ref ID J:105528)
  • as early as P7, homozygotes spontaneously roll on their backs more often than wild type mice, have difficuly righting themselves when placed on their backs, and are unable to swim
  • following unilateral labyrinthectomy, homozygotes fail to exhibit the expected oculomotor and postural changes (i.e. ocular nystagmus and static postural syndromes) observed in wild type mice
• circling (MGI Ref ID J:105528)
  • following unilateral labyrinthectomy, homozygotes continue to circle instead of exhibiting the expected static postural syndromes
  • unlike wild type mice, homozygotes cannot walk or run in a straight path in an open field or on a treadmill, and exhibit episodes of spontaneous circling during which the vertebral column maintains an S-shaped posture
• bi-directional circling (MGI Ref ID J:105528)
  • as mice mature, exhibit an intermittent bidirectional circling behavior
• unidirectional circling (MGI Ref ID J:105528)
  • interestingly, with time circling tends to become more unidirectional
• head bobbing (MGI Ref ID J:37461)
  • when at rest (i.e. alert but stationary), homozygotes show intermittent episodes of head bobbing with the head oscillating in the sagittal plane about the atlanto-occipital joint by 10-30° at 3-5 Hz
• head tilt (MGI Ref ID J:37461)
  • occasional head tilt
• absent pinna reflex (MGI Ref ID J:105528)
  • fail to show any pinnea reflex
• absent startle reflex (MGI Ref ID J:37461)
  • fail to show signs of startle
• absent vestibuloocular reflex (MGI Ref ID J:105528)
  • vestibulo-ocular reflex (VOR) testing indicates that head rotation fails to elicit compensatory slow-phase eye movements in mutant mice; no vestibular quick phases are generated at low frequencies
  • VOR gain is statistically insignificant at all frequencies and both velocities examined
• decreased startle reflex (MGI Ref ID J:105528)
• abnormal semicircular canal (MGI Ref ID J:105528)
  • at 5 months, the semicircular canals appear largely abnormal
• abnormal crista ampullaris morphology (MGI Ref ID J:37461)
  • hair cells of the cristae degenerate postnatally, beginning at P10
  • at 5 months, the cristae exhibit massive degeneration at the level of hair cells and in the transitional epithelium while the core of the cristae appears vacuolated
  • in contrast, no degeneration in vestibular nerve fibers or cells in Scarpa's ganglion is observed
• abnormal neuroepithelium of ampullary crest (MGI Ref ID J:108905)
  • at P22, but not earlier, the general morphology of sensory hair cells (type I and II) is relatively normal, except for the presence of intracytoplasmic rods or filaments and of a few cystic cavities surrounded by an afferent nerve calyx
  • however, the nucleus is not pyknotic and hair bundles are present through scattered in some cases
• abnormal vestibule morphology (MGI Ref ID J:37461)
  • exhibit a collapse of the vestibular wall at P3, indicating a decrease in endolymph volume
  • the transitional epithelium and the inner core of the cristae are degenerating by P42 and by 7 months of age, no structure is discerned within the ampullae
  • the melanocyte and dark cell layer are twisted and displaced toward the epithelial surface of the cristae at P42
  • loss of connective tissue that normally underlies the vestibule by P42
  • vestibular dark cells begin to degenerate at P3 and connective tissue below the dark cell epithelium is less abundant
  • the apical membrane surface of the dark cell epithelial layer of the vestibular labyrinth is jagged and scalloped rather than smooth
  • by P69, vestibular end-organs have completely degenerated, although vestibular dark cells are still present
• abnormal vestibular dark cell morphology (MGI Ref ID J:77288)
  • the melanocyte and dark cell layer are twisted and displaced toward the epithelial surface of the cristae at P42
  • the apical membrane surface of the dark cell epithelial layer of the vestibular labyrinth is jagged and scalloped rather than smooth
  • although normal at birth, the basal membrane infoldings and size of vestibular dark cells start to increase at P7
  • at P10, the height and volume of dark cells is increased, the cytoplasm and nucleus are restricted to the apical side facing the endolymph, and basolateral membrane infoldings occupy >2/3 of cell height
  • at P22, dark cells show significant increases in cell size, multiplication of mitochondria and basal membrane infoldings; the cytoplasm is reduced to a tiny area around a pyknotic nucleus and extracellular spaces between the infoldings are dilated
  • by P69, the cells of the roof of the ampullae are crushed onto the dark cells and the endolymphatic space has completely collapsed
  • at P69, vestibular dark cells are still present but morphologically resemble those observed at 1 or 3 weeks after birth, except for a pyknotic nucleus
• vestibular dark cell degeneration (MGI Ref ID J:77288)
  • vestibular dark cells begin to degenerate at P3 and connective tissue below the dark cell epithelium is less abundant
• saccular macula degeneration (MGI Ref ID J:105528)
  • at 5 months, the macule of the saccule shows significant, though less striking, signs of degeneration
• utricular macular degeneration (MGI Ref ID J:105528)
  • at 5 months, the macule of the utricle shows significant, though less striking, signs of degeneration
• vestibular hair cell degeneration (MGI Ref ID J:37461)
  • hair cells of the macula of the sacculus degenerate postnatally, beginning around 5 months of age
  • by P69, most vestibular hair cells have degenerated and the space between the afferent calyx and cells is enlarged
  • at P69, rare remaining sensory hair cells appear completely wrapped in a few remaining supporting cells
• nervous system phenotype
• cochlear ganglion degeneration (MGI Ref ID J:37461)
  • first signs of spiral ganglion cell degeneration in the cochlea occur at P20, with the majority degenerated by P42, however do not see loss of apical ganglion cells
• cochlear hair cell degeneration (MGI Ref ID J:37461)
  • hair cells of the cochlear duct differentiate normally but degenerate postnatally, starting at around P3
• vestibular hair cell degeneration (MGI Ref ID J:37461)
  • hair cells of the macula of the sacculus degenerate postnatally, beginning around 5 months of age
  • by P69, most vestibular hair cells have degenerated and the space between the afferent calyx and cells is enlarged
  • at P69, rare remaining sensory hair cells appear completely wrapped in a few remaining supporting cells
• cardiovascular system phenotype
• prolonged QT interval (MGI Ref ID J:77288)
• digestive/alimentary phenotype
• abnormal digestive system physiology (MGI Ref ID J:77288)
  • fecal potassium excretion increases linearly with plasma potassium concentration much more rapidly than in wild type, indicating a dysfunction of the intestine in secreting or absorbing potassium
• abnormal feces composition (MGI Ref ID J:77288)
  • mutants fed a normal, high, or low potassium diet excrete per gram of feces, respectively,1.9-, 1.8-, and 1.8-fold as much sodium and 2.2-, 1.8-, or 1.4-fold as much potassium as wild type
• hematopoietic system phenotype
• increased hematocrit (MGI Ref ID J:77288)
• homeostasis/metabolism phenotype
• abnormal blood chemistry (MGI Ref ID J:77288)
  • increase in plasma osmolality
• abnormal circulating renin level (MGI Ref ID J:77288)
  • renin levels are not decreasaed by a high potassium diet as in wild type
• hypokalemia (MGI Ref ID J:77288)
  • hypokalemia is seen on a normal (0.9%) and high (3%) potassium diet, but not a low (0.05%) potassium diet
• increased circulating aldosterone level (MGI Ref ID J:77288)
  • higher plasma levels on both a normal and high potassium diet
• increased circulating chloride level (MGI Ref ID J:77288)
• increased circulating sodium level (MGI Ref ID J:77288)
• dehydration (MGI Ref ID J:77288)
  • slightly dehydrated