Phenotypes Associated with This Genotype

Genotype
MGI:8215454

• Allelic Composition: Piezo1^em1Dbee/Piezo1^em1Dbee
• Genetic Background: C57BL/6-Piezo1^em1Dbee

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

mortality/aging

prenatal lethality, incomplete penetrance ( J:368272 )

• mice are born at a slightly lower frequency than wild-type mice

growth/size/body

increased spleen weight ( J:368272 )

• mice at 22 weeks of age show increased spleen weight, however 8-week-old mice show normal spleen weight indicating an age-related increase in spleen weight

hematopoietic system

increased spleen weight ( J:368272 )

• mice at 22 weeks of age show increased spleen weight, however 8-week-old mice show normal spleen weight indicating an age-related increase in spleen weight

decreased erythrocyte cell number ( J:368272 )

• seen at 8 weeks of age; all phenotypes reported were observed at 8 weeks of age, unless otherwise specified

decreased hematocrit ( J:368272 )

increased hemoglobin concentration distribution width ( J:368272 )

decreased hemoglobin content ( J:368272 )

increased red blood cell distribution width ( J:368272 )

stomatocytosis ( J:368272 )

reticulocytosis ( J:368272 )

• increase in percentage of reticulocytes

abnormal erythrocyte physiology ( J:368272 )

• resting membrane potential of RBCs is slightly hyperpolarized

• membrane potential recordings using patch-clamp on RBCs shows that depolarization in response to sheer stress (i.e. fluid flow) is larger in RBCs and there is a failure to recover after flow ceases

• ionic current recordings using voltage-clamp shows that initial response of RBC to fluid flow is similar to wild-type except for the absence of slow inactivation and a failure of current to recover after cessation of fluid flow

• single-channel activity of RBCs measured by the cell-attached patch technique shows higher activity after termination of pressure pulses, with frequency of open-state activity higher relative to the closed-state frequency, indicating persistent activity and failure of deactivation in single channels

• GsMTx4, an inhibitor or PIEZO1 channel activity, abolishes all depolarizing and inward current activities in RBCs but interestingly, washout of GsMTx4 shows recovery of activity that is more like the activity of wild-type RBCs than mutant RBCs in the absence of toxin

decreased erythrocyte osmotic fragility ( J:368272 )

homeostasis/metabolism

increased circulating transferrin level ( J:368272 )

• small increase in transferrin

• while there are potential changes in plasma iron and total iron binding capacity but they do no reach statistical significance

immune system

increased spleen weight ( J:368272 )

• mice at 22 weeks of age show increased spleen weight, however 8-week-old mice show normal spleen weight indicating an age-related increase in spleen weight

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dehydrated hereditary stomatocytosis 1		DOID:0111576	OMIM:194380	J:368272