Phenotypes associated with this allele

• Allele Symbol: Add2^tm1Llp
• Allele Name: targeted mutation 1, Luanne L Peters
• Allele ID: MGI:2149065
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Add2^tm1Llp/Add2^tm1Llp	B6.129S4-Add2^tm1Llp/LlpJ	MGI:3664938
hm2	Add2^tm1Llp/Add2^tm1Llp	involves: 129S4/SvJae * C57BL/6J	MGI:3664740
cx3	Add2^tm1Llp/Add2^tm1Llp Add3^tm1.2Llp/Add3^tm1.2Llp	involves: 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6J * FVB/N	MGI:4462409

Genotype
MGI:3664938

hm1

• Allelic Composition: Add2^tm1Llp/Add2^tm1Llp
• Genetic Background: B6.129S4-Add2^tm1Llp/LlpJ

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

behavior/neurological

abnormal contextual conditioning behavior ( J:98208 )

• exhibit impaired performance on the contextual fear conditioning task, showing decreased freezing in response to the context-paired previously with foot shock cue

abnormal cued conditioning behavior ( J:98208 )

• exhibit impaired performance on cued fear conditioning task showing decreased freezing in response to the shock-paired auditory cue

abnormal spatial learning ( J:98208 )

• exhibit impaired performance in the water maze as shown by increased travel distance before finding the platform and slightly longer time to find the platform on the second and subsequent training days

• in a probe trial, spend equivalent amounts of time in each quadrant compared to wild-type which spend 50% of the time in the quadrant containing the platform

nervous system

impaired synaptic plasticity ( J:98208 )

• CA1 short- and long-term synaptic plasticity is impaired, with significantly stronger input-output relationships in hippocampal slices

abnormal CNS synaptic transmission ( J:98208 )

reduced long-term potentiation ( J:98208 )

• show impaired tetanic long-term potentiation in the SC-CA1 hippocampal circuit

increased post-tetanic potentiation ( J:98208 )

• immediately after two 1 s trains of 100 Hz stimulation, post-tetanic potential is slightly more robust than in wild-type hippocampal slices, and responses decay to baseline within 90 min while they remain potentiated for the duration of the experiment in wild-type

enhanced paired-pulse facilitation ( J:98208 )

• exhibit slightly enhanced paired-pulse facilitation at the 150s interstimulus interval

Genotype
MGI:3664740

hm2

• Allelic Composition: Add2^tm1Llp/Add2^tm1Llp
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

Red blood cell and histological spleen comparison of Add2^tm1Llp/Add2^tm1Llp and +/+ wildtype mouse.

growth/size/body

enlarged spleen ( J:71029 )

hematopoietic system

enlarged spleen ( J:71029 )

anemia ( J:71029 , J:161920 )

abnormal erythrocyte morphology ( J:161920 )

• the amount of alpha adducin in red blood cell membranes is reduced to 20% of normal levels while there is a 5-fold increase in gamma adducin and there are many red blood cells of reduced size and abnormal shapes including spherocytes, spherostomatocytes, and rounded elliptocytes

decreased hematocrit ( J:71029 , J:161920 )

• hematocrit of 47.8% compared with 51.4% in wild-type controls (J:161920)

increased mean corpuscular hemoglobin concentration ( J:71029 )

decreased mean corpuscular volume ( J:71029 )

anisopoikilocytosis ( J:71029 , J:161920 )

• red blood cells are smaller and show a variety of shapes, including spehrocytes, spherostomatocytes, and rounded elliptocytes (J:71029)

microcytosis ( J:71029 )

• red blood cells are smaller

spherocytosis ( J:71029 , J:161920 )

reticulocytosis ( J:71029 , J:161920 )

• reticulocyte percentages are increased, indicating a compensatory acceleration of red blood cell production in response to chronic hemolysis (J:71029)

• the reticulocyte percentage is increased to 4.3% versus 2.8% in wild-type controls (J:161920)

increased spleen iron level ( J:71029 )

• iron deposition is increased in the spleen

abnormal erythrocyte physiology ( J:71029 )

• red blood cells are osmotically fragile and dehydrated (as indicated by decreased potassium and sodium content)

• red blood cells show decreased levels of alpha-adducin (Add1) and increased levels of gamma-adducin (Add3)

increased erythrocyte osmotic fragility ( J:161920 )

• increased red blood cell fragility as assessed by both osmotic lysis and ektacytometry

homeostasis/metabolism

increased spleen iron level ( J:71029 )

• iron deposition is increased in the spleen

increased kidney iron level ( J:71029 )

• iron deposition is increased in the kidney

increased liver iron level ( J:71029 )

• iron deposition is increased in the liver

immune system

enlarged spleen ( J:71029 )

increased spleen iron level ( J:71029 )

• iron deposition is increased in the spleen

liver/biliary system

increased liver iron level ( J:71029 )

• iron deposition is increased in the liver

renal/urinary system

increased kidney iron level ( J:71029 )

• iron deposition is increased in the kidney

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hereditary spherocytosis type 1		DOID:0110916	OMIM:182900	J:71029

Genotype
MGI:4462409

cx3

• Allelic Composition: Add2^tm1Llp/Add2^tm1Llp; Add3^tm1.2Llp/Add3^tm1.2Llp
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6J * FVB/N

hematopoietic system

anemia ( J:161920 )

abnormal erythrocyte morphology ( J:161920 )

• additional disruption of the gamma adducin gene does not exacerbate the phenotype of the beta adducin knockout and the changes in hematological values, altered red blood cell shapes and size, reticulocytosis, decreased hematocrit, and increased red blood cell fragility are the same, although the alpha adducin levels in red blood cell membranes is reduced to an almost undetectable level and the level in brain and spleen is reduced to half normal levels

decreased hematocrit ( J:161920 )

decreased mean corpuscular volume ( J:161920 )

anisopoikilocytosis ( J:161920 )

spherocytosis ( J:161920 )

reticulocytosis ( J:161920 )

increased erythrocyte osmotic fragility ( J:161920 )

• the increase in red blood cell fragility as assessed by osmotic lysis and ektacytometry is the same as in beta adducin knockouts