Phenotypes Associated with This Genotype

Genotype
MGI:3663255

• Allelic Composition: S1pr2^tm1Ajml/S1pr2^tm1Ajml
• Genetic Background: involves: 129S5/SvEvBrd * C57BL/6

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

nervous system

seizures ( J:73957 )

• unexpectedly, homozygotes display normal brain cytoarchitecture, peripheral axon growth and neurological development, with no postnatal motor/sensory dysfunction or defects in hippocampal and neocortical development

• however, between 3 and 7 wks of age, homozygotes display spontaneous, intermittent sporadic seizures of variable timing occurring in clusters of 3 or more per hr during 1-4-day periods within the susceptible interval

• ~85% of seizures are characterized by 2-10-sec wild running episodes followed by 15-60-sec periods of freezing

• the vast majority of severely affected homozygotes survive the susceptible period and recover

tonic-clonic seizures ( J:73957 )

• ~15% of seizures are characterized by 2-10 sec wild running episodes followed by tonic-clonic convulsions; 2% of these are lethal

abnormal nervous system electrophysiology ( J:73957 )

abnormal action potential ( J:73957 )

• under current clamp, 10 of 14 mutant neocortical pyramidal neurons exhibit spontaneous paroxysmal depolarizing shifts and bursts of action potentials

• addition of GABA_A receptor antagonist bicuculline methiodide increases burst frequency and results in a prolonged depolarization with repetitive action potentials in 4 of the cells

• in the presence of bicuculline, electrically evoked epileptiform depolarization responses are augmented in mutant cells relative to wild-type cells

abnormal brain wave pattern ( J:73957 )

• spontaneous seizures are accompanied by ictal-like EEG abnormalities and hyperexcitable neocortical pyramidal neurons

abnormal CNS synaptic transmission ( J:73957 )

abnormal excitatory postsynaptic currents ( J:73957 )

• homozygotes show significant increases in both the frequency and amplitude of spontaneous EPSCs

• the ampliture of electrically evoked EPSCs is also markedly increased in the absence of pharmacological or ionic enhancement

increased excitatory postsynaptic current amplitude ( J:73957 )

• of spontaneous EPSCs

increased excitatory postsynaptic current frequency ( J:73957 )

• of spontaneous EPSCs

behavior/neurological

seizures ( J:73957 )

• unexpectedly, homozygotes display normal brain cytoarchitecture, peripheral axon growth and neurological development, with no postnatal motor/sensory dysfunction or defects in hippocampal and neocortical development

• however, between 3 and 7 wks of age, homozygotes display spontaneous, intermittent sporadic seizures of variable timing occurring in clusters of 3 or more per hr during 1-4-day periods within the susceptible interval

• ~85% of seizures are characterized by 2-10-sec wild running episodes followed by 15-60-sec periods of freezing

• the vast majority of severely affected homozygotes survive the susceptible period and recover

tonic-clonic seizures ( J:73957 )

• ~15% of seizures are characterized by 2-10 sec wild running episodes followed by tonic-clonic convulsions; 2% of these are lethal

hematopoietic system

increased germinal center B cell number ( J:154439 )

• increase in germinal center B cells in 9-12 month old mice before tumor formation

increased T cell number ( J:154439 )

• increase in germinal center CD69+ T cells in 9-12 month old mice before tumor formation

increased spleen germinal center number ( J:154439 )

• spleens show an increase in number of spontaneous germinal centers at 9-12 months of age before tumor formation

increased spleen germinal center size ( J:154439 )

• spleens show an increase in size of spontaneous germinal centers at 9-12 months of age before tumor formation

abnormal spleen marginal zone morphology ( J:154439 )

• benign splenic marginal zone hyperplasia

immune system

increased germinal center B cell number ( J:154439 )

• increase in germinal center B cells in 9-12 month old mice before tumor formation

increased T cell number ( J:154439 )

• increase in germinal center CD69+ T cells in 9-12 month old mice before tumor formation

increased spleen germinal center number ( J:154439 )

• spleens show an increase in number of spontaneous germinal centers at 9-12 months of age before tumor formation

increased spleen germinal center size ( J:154439 )

• spleens show an increase in size of spontaneous germinal centers at 9-12 months of age before tumor formation

abnormal spleen marginal zone morphology ( J:154439 )

• benign splenic marginal zone hyperplasia

neoplasm

increased B cell derived lymphoma incidence ( J:154439 )

• mice develop clonal B-cell lymphomas with age, such that 50% of mice show neoplasm by 1.5-2 years of age

• tumors show features of germinal center-derived diffuse large B-cell lymphoma

• tumors are seen in mesenteric, submandibular, and mediastinal lymph nodes, in the spleen, and rarely in the liver and retroperitoneal soft tissue, with frequent involvement of multiple sites within individual mice

increased lung tumor incidence ( J:154439 )

• a very low incidence of lung tumors is seen and these are adenocarcinomas or very large lung adenoma classified as carcinoma due to size

respiratory system

increased lung tumor incidence ( J:154439 )

• a very low incidence of lung tumors is seen and these are adenocarcinomas or very large lung adenoma classified as carcinoma due to size

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
non-Hodgkin lymphoma		DOID:0060060	OMIM:605027	J:154439