Phenotypes associated with this allele

• Allele Symbol: Aqp4^tm1Ask
• Allele Name: targeted mutation 1, Alan S Verkman
• Allele ID: MGI:1857808
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Aqp4^tm1Ask/Aqp4^tm1Ask	B6.Cg-Aqp4^tm1Ask	MGI:3655808
hm2	Aqp4^tm1Ask/Aqp4^tm1Ask	involves: C57BL/6J	MGI:2174935
hm3	Aqp4^tm1Ask/Aqp4^tm1Ask	involves: C57BL/6J * CD-1	MGI:3655806
cx4	Aqp3^tm1Ask/Aqp3^tm1Ask Aqp4^tm1Ask/Aqp4^tm1Ask	involves: C57BL/6J	MGI:2655442
cx5	Aqp3^tm1Ask/Aqp3^tm1Ask Aqp4^tm1Ask/Aqp4^tm1Ask	involves: C57BL/6J * CD-1	MGI:3783407
cx6	Aqp1^tm1Ask/Aqp1^tm1Ask Aqp4^tm1Ask/Aqp4^tm1Ask	involves: C57BL/6J * CD-1	MGI:3783422

Genotype
MGI:3655808

hm1

• Allelic Composition: Aqp4^tm1Ask/Aqp4^tm1Ask
• Genetic Background: B6.Cg-Aqp4^tm1Ask

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

hearing/vestibular/ear

deafness ( J:71154 )

• Background Sensitivity: hearing loss is more severe than in mice on a mixed C57BL/6 and CD-1 background

• on a congenic C57BL/6 background almost all mice are deaf

vision/eye

abnormal eye electrophysiology ( J:109783 )

• Background Sensitivity: b-wave amplitude and oscillatory potentials are reduced in mice on a C57BL/6 background but not in mice on a mixed CD-1 and C57BL/6 background

retina ischemia ( J:109783 )

• ischemia-induced impairment of b wave and oscillatory potential amplitudes is reduced compared to wild-type mice

• ischemia-induced decreases in retinal thickness and cellularity are reduced compared to wild-type mice; however, prior to ischemia no differences in retinal morphology are seen

Genotype
MGI:2174935

hm2

• Allelic Composition: Aqp4^tm1Ask/Aqp4^tm1Ask
• Genetic Background: involves: C57BL/6J

renal/urinary system

decreased urine osmolality ( J:42704 , J:46296 )

• urine osmolality is similar to wild-type when water is freely available but maximum urine osmolality is reduced following 36 hours of water deprivation (J:42704)

• however, kidney morphology is similar to wild-type (J:42704)

• after 36 hour water deprivation or intraperitoneal injection of desmopressin (J:46296)

abnormal renal water transport ( J:46296 )

• osmotic water permeability of inner medullary collecting ducts is decreased to 13.1 +/- 3.7 cm/s x 10^-3 compared to 56.0 +/- 8.5 cm/s x 10^-3 in wild-type mice

vision/eye

abnormal eye electrophysiology ( J:74263 )

• at 10 months of age b-wave amplitudes and latencies are reduced; however, no differences in retinal morphology are detected

homeostasis/metabolism

decreased urine osmolality ( J:42704 , J:46296 )

• urine osmolality is similar to wild-type when water is freely available but maximum urine osmolality is reduced following 36 hours of water deprivation (J:42704)

• however, kidney morphology is similar to wild-type (J:42704)

• after 36 hour water deprivation or intraperitoneal injection of desmopressin (J:46296)

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:56302 )

N • homozygotes display no defects in the volume or composition of saliva, as revealed by pilocarpine stimulation studies

Genotype
MGI:3655806

hm3

• Allelic Composition: Aqp4^tm1Ask/Aqp4^tm1Ask
• Genetic Background: involves: C57BL/6J * CD-1

mortality/aging

decreased susceptibility to induced morbidity/mortality ( J:111923 )

• following intraperitoneal water infusion to induce water intoxication most wild-type mice become uncoordinated within 10 minutes, rapidly progress to paralysis and by 60 minutes 92% are dead compared to homozygotes which develop only mild lethargy with 76% surviving after 60 minutes

hearing/vestibular/ear

abnormal auditory brainstem response waveform shape ( J:71154 )

• at 4-5 weeks, the amplitudes of wave I are significantly decreased at click intensities of 70, 60, and 50 dB relative to wild-type; however, the organ of Corti remains intact with clearly demarcated hair cells and supportive cells

increased or absent threshold for auditory brainstem response ( J:71154 , J:79863 )

• at 4-5 weeks of age, homozygotes exhibit a significantly increased ABR threshold by >12 db relative to wild-type mice (J:71154)

• at 12 weeks of age, homozygotes of a predominantly CD-1 background exhibit a >2.5-fold elevation in average ABR thresholds to both broadband and tone-specific stimuli relative to wild-type mice (37 dB SPL vs 14 dB SPL, respectively) (J:79863)

• however, no significant differences in the latency period for all major peaks are observed in response to tone specific stimuli, indicating normal neural conduction times (J:79863)

impaired hearing ( J:71154 )

• Background Sensitivity: hearing loss is less severe than in mice on a coisogenic C57BL/6 background which are almost all deaf

unilateral deafness ( J:79863 )

• unlike wild-type mice, homozygotes show a significantly higher inter-ear variability or bilateral asymmetry, as assessed by ABR thresholds

• 2 of 7 homozygotes exhibit extreme bilateral asymmetry in auditory function, with one ear displaying an ABR threshold of 15 dB (i.e. intact hearing), while the other ear displays a threshold of 50 dB (auditory dysfunction)

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:63987 , J:111923 )

N • serum gastrin levels are similar to wild-type (J:63987)

N • serum sodium concentration and osmolality are similar to wild-type (J:111923)

abnormal fluid regulation ( J:111923 )

• following intraperitoneal water infusion to induce water intoxication pericapillary astrocytic foot process swelling in the brain is reduced and the increase in brain water content is decreased compared to wild-type mice

decreased susceptibility to ischemic brain injury ( J:111923 )

• following middle cerebral artery occlusion mortality rate, neurological deficit scores, brain edema, and infarct volume are all decreased compared to wild-type mice

nervous system

nervous system phenotype ( J:111923 )

N • no gross abnormalities are seen in brain morphology and the blood-brain barrier is intact

decreased susceptibility to ischemic brain injury ( J:111923 )

• following middle cerebral artery occlusion mortality rate, neurological deficit scores, brain edema, and infarct volume are all decreased compared to wild-type mice

digestive/alimentary system

digestive/alimentary phenotype ( J:63987 )

N • gastric pit morphology and gastric acid output are similar to wild-type

vision/eye

vision/eye phenotype ( J:62579 , J:109783 )

N • basal and pilocarpine-stimulated tear production and chloride concentration are similar to wild-type (J:62579)

N • Background Sensitivity: b-wave amplitude and oscillatory potentials are reduced in mice on a C57BL/6 background but not in mice on a mixed CD-1 and C57BL/6 background (J:109783)

retina ischemia ( J:109783 )

• ischemia-induced impairment of b wave and oscillatory potential amplitudes is reduced compared to wild-type mice

• ischemia-induced decreases in retinal thickness and cellularity are reduced compared to wild-type mice; however, prior to ischemia no differences in retinal morphology are seen

behavior/neurological

behavior/neurological phenotype ( J:111923 )

N • no behavioral, motor sensory, or coordination abnormalities are detected

cardiovascular system

cardiovascular system phenotype ( J:111923 )

N • morphology of the posterior, anterior and middle cerebral arteries is similar to wild-type

Genotype
MGI:2655442

cx4

• Allelic Composition: Aqp3^tm1Ask/Aqp3^tm1Ask; Aqp4^tm1Ask/Aqp4^tm1Ask
• Genetic Background: involves: C57BL/6J

renal/urinary system

decreased urine osmolality ( J:61675 )

• urine osmolality is decreased when given free access to water and the increase in osmolality induced by 36 hour water deprivation or 1-desamino-8-D-arginine-vasopressin treatment is less than that in Aqp3 single homozygotes

polyuria ( J:61675 )

homeostasis/metabolism

decreased urine osmolality ( J:61675 )

• urine osmolality is decreased when given free access to water and the increase in osmolality induced by 36 hour water deprivation or 1-desamino-8-D-arginine-vasopressin treatment is less than that in Aqp3 single homozygotes

Genotype
MGI:3783407

cx5

• Allelic Composition: Aqp3^tm1Ask/Aqp3^tm1Ask; Aqp4^tm1Ask/Aqp4^tm1Ask
• Genetic Background: involves: C57BL/6J * CD-1

respiratory system

abnormal respiratory system physiology ( J:106285 )

• small (2-5%), significant reduction in lower airway humidification relative to wild-type

• 3-9% impairment of upper airway humidification compared to controls

Genotype
MGI:3783422

cx6

• Allelic Composition: Aqp1^tm1Ask/Aqp1^tm1Ask; Aqp4^tm1Ask/Aqp4^tm1Ask
• Genetic Background: involves: C57BL/6J * CD-1

growth/size/body

postnatal growth retardation ( J:106259 )

• mice grow 15-20% slower than wild-type animals

respiratory system

abnormal respiratory system physiology ( J:106259 )

• lower rate of water transport in lungs relative to Aqp1-null animals is measured

cardiovascular system

decreased vascular permeability ( J:106259 )

• airspace-capillary water permeability in lungs is reduced compared to Aqp1-null mice

• water permeability is 15-fold lower than in wild-type lungs