Phenotypes associated with this allele

• Allele Symbol: Trpv4^tm1Rck
• Allele Name: targeted mutation 1, J M Friedman
• Allele ID: MGI:2682656
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Trpv4^tm1Rck/Trpv4^tm1Rck	involves: C57BL/6	MGI:5009033
hm2	Trpv4^tm1Rck/Trpv4^tm1Rck	Not Specified	MGI:2682662

Genotype
MGI:5009033

hm1

• Allelic Composition: Trpv4^tm1Rck/Trpv4^tm1Rck
• Genetic Background: involves: C57BL/6

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

behavior/neurological

behavior/neurological phenotype ( J:127385 )

N • mice exhibit normal behavior and anxiety-related behavior

abnormal nociception after inflammation ( J:107380 )

• after intraplantar injection of inflammatory soup, mice exhibit a 2.8-fold decrease in frequency of paw withdrawal compared with wild-type mice

abnormal pain threshold ( J:107380 )

• following injection of prostaglandin E2 (PGE2) and serotonin (5-HT), frequency of paw withdrawal is less than in wild-type mice

• pre-treatment with 8-bromoadenosine 3', 5'-cAMP (8-Br-cAMP), PGE2-induced increase in paw withdrawal response frequency is absent unlike in wild-type mice

• cAMP-dependent protein kinase A catalytic subunit- (PKACS) or psi/epsilon-RACK-induced increase in frequency paw withdrawal is absent unlike in wild-type mice

renal/urinary system

abnormal urinary bladder physiology ( J:127385 )

• urothelial cells fail to exhibit response to 4 alpha-phorbol-12,13-didecanoate, arachidonic acid unlike wild-type cells

• bladder strips exhibit abnormal spontaneous contractility compared with wild-type bladder stripes

• isolated whole bladders exhibit decreased stretch-evoked intravesical ATP release compared with wild-type bladders

• mice exhibit lower frequency of voiding contractions and higher frequency of nonvoiding contractions compared with wild-type mice

• however, response to hypertonic solution is normal

urinary incontinence ( J:127385 )

• mice exhibit more disperse urine voiding pattern with multiple urine spots away from the corners compared with wild-type mice

nervous system

abnormal neuron physiology ( J:107380 )

• hypotonicity induces a smaller increase in intracellular calcium compared to in wild-type neurons

• following treatment with inflammatory soup, neurons fail to exhibit enhanced hypotonicity-induced increase in free calcium unlike in wild-type mice

• following treatment with inflammatory soup, neurons exhibit a 1.6-fold decrease in intracellular calcium levels compared with wild-type mice

• hypotonicity-induced intracellular calcium is not reduced by treatment with a PKC epsilon translocation inhibitor peptide unlike in wild-type neurons

Genotype
MGI:2682662

hm2

• Allelic Composition: Trpv4^tm1Rck/Trpv4^tm1Rck
• Genetic Background: Not Specified

Trpv4^tm1Rck/Trpv4^tm1Rck mice show protection from UVB-induced skin injury

behavior/neurological

behavior/neurological phenotype ( J:86560 , J:200749 )

N • homozygotes show no differences in withdrawal latencies for noxious heat stimuli relative to wild-type littermates (3.78 sec vs. 3.8 sec, respectively), indicating that thermal nociception is intact (J:86560)

N • chemical irritant-induced nocifensive behavior is similar to controls (J:200749)

abnormal drinking behavior ( J:86560 )

• in response to systemic osmotic challenge with 0.5 M NaCl (i.p. administration), single-housed homozygotes without food and water show a significant delay in the initiation of drinking behavior relative to similarly-treated wild-type mice (5.0 min vs. 3.2 min, respectively)

decreased fluid intake ( J:86560 )

• when single-housed with no access to food, unchallenged homozygotes show a significantly reduced water intake which is most pronounced in the first 6 hrs of the experiment; after 24 hrs, fluid consumption is <70% of that in wild-type littermates (1.4 vs. 2.2 ml, respectively)

• in response to systemic osmotic challenge with 0.5 M NaCl (i.p. administration), single-housed homozygotes without food and water show a significantly reduced amount of water intake relative to similarly-treated wild-type mice

• notably, chronic infusion of dDAVP (an ADH analogue) reduces the amounts of drinking by 49% in wild-type (1.22 ml per 30 hrs) vs. only 23% in mutant mice (1.61 ml per 30 hrs) with no significant differences in urine osmolality between the two groups, indicating an impaired response to hypoosmolar stimulation but a normal response to ADH

abnormal mechanical nociception ( J:86560 , J:200749 )

• homozygotes display a reduced response to noxious mechanical stimuli relative to wild-type littermates (J:86560)

• decrease in sensitivity toward noxious mechanical stimulation 48 hours after UV exposure compared to similarly treated controls (J:200749)

increased thermal nociceptive threshold ( J:200749 )

• decrease in sensitivity toward noxious radiant heat stimulation 48 hours after UV exposure compared to similarly treated controls

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:86560 )

N • homozygotes display normal basal body temperatures with no significant differences in mean body temperature after a cold stress test at 4C for 150 min (35.86 vs. 35.36C in wild-type vs. mutant)

decreased blood osmolality ( J:86560 )

• in response to chronic systemic administration of an ADH analogue (dDAVP), where mice are single-housed, water is freely available and food is withheld for 24 hrs, homozygotes become significantly hypotonic whereas wild-type mice remained normotonic (286 vs. 294 milliosmol/kg, respectively)

increased blood osmolality ( J:86560 )

• when homozygotes are single-housed without food and free access to water, they show a slight but significant increase in blood osmolality relative to similarly-treated wild-type mice (295 vs. 300 milliosmol/kg at 24 hrs, respectively)

• however, normal systemic osmotic pressure is observed in both genotypes when mice are group-housed with freely available food and water

• in response to dehydration, single-housed homozygotes with no access to food and water show a significant rise of blood osmolality after 48 hrs of water deprivation relative to wild-type mice (318 vs. 305 milliosmol/kg, respectively)

• in response to systemic osmotic challenge with an i.p. injection of a hyperosmotic solution (0.5 M NaCl, 0.8 ml per 20 g of body weight), single-housed homozygotes without food and water show a significantly higher systemic osmotic pressure relative to wild-type mice (334.3 vs. 325.9 milliosmol/kg, respectively), indicating impaired defense against hypertonicity

decreased circulating antidiuretic hormone level ( J:86560 )

• in response to systemic hypertonic challenge with i.p. administration of 0.15 and 0.5M NaCl, single-housed homozygotes without food and water show significantly lower plasma ADH levels than wild-type mice (4.2 vs. 3.4 pg/ml for 0.15 M NaCl; 34.1 vs. 23 pg/ml for 0.5 M NaCl, respectively)

abnormal fluid regulation ( J:86560 )

• homozygotes exhibit abnormal osmotic sensing in the central nervous system, with impaired responses to both hyper- and hypoosmolar stimuli

• after a hyperosmolar challenge, homozygotes show a significantly reduced expression of Fos in the circumventricular organ, the organum vasculosum of the lamina terminalis

decreased susceptibility to injury ( J:126500 )

• lungs lack 4 alpha-phorbol-12,13-didecanoate-induced endothelial permeability unlike in wild-type mice

• however, response to thapsigargin is normal

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:86560 )

N • homozygotes display normal inner ear function, with no significant differences in the acoustic startle response or any obvious abnormalities indicative of vestibular dysfunction relative to wild-type mice

integument

abnormal keratinocyte physiology ( J:200749 )

• primary epidermal keratinocytes show a greatly diminished UVB-mediated Ca2+ response

respiratory system

abnormal respiratory system physiology ( J:126500 )

• lungs lack 4 alpha-phorbol-12,13-didecanoate-induced endothelial permeability unlike in wild-type mice

• however, response to thapsigargin is normal

cardiovascular system

abnormal vascular endothelial cell physiology ( J:129365 )

• in response to 4 alpha-phorbol-12,13-didecanoate, arachidonic acid, and hypotonicity, carotid artery endothelial cells fail to exhibit cationic currents compared with wild-type cells

abnormal vasodilation ( J:129365 )

• mice fail to exhibit 4 alpha-phorbol-12,13-didecanoate-induced vasodilation compared with wild-type mice

• mice fail to exhibit shear stress-induced vasodilation unlike wild-type mice

• mice exhibit reduced reperfusion-induced vasodilation compared with wild-type mice

• however, mice exhibit normal acetylcholine-induced and endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilation

muscle

abnormal vasodilation ( J:129365 )

• mice fail to exhibit 4 alpha-phorbol-12,13-didecanoate-induced vasodilation compared with wild-type mice

• mice fail to exhibit shear stress-induced vasodilation unlike wild-type mice

• mice exhibit reduced reperfusion-induced vasodilation compared with wild-type mice

• however, mice exhibit normal acetylcholine-induced and endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilation

vision/eye

abnormal trabecular meshwork morphology ( J:216400 )

• primary cilia in the trabecular meshwork are shortened

ocular hypertension ( J:216400 )

• intraocular pressure (IOP) is elevated