Phenotypes associated with this allele

• Allele Symbol: Slc12a5^tm2Hsav
• Allele Name: targeted mutation 2, Harri Savilahti
• Allele ID: MGI:5638435
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Slc12a5^tm2Hsav/Slc12a5^tm2Hsav	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:5638536
ht2	Slc12a5^tm1Hsav/Slc12a5^tm2Hsav	involves: 129S1/Sv * 129S2/SvPasHsd * 129X1/SvJ * C57BL/6J * C57BL/6JOlaHsd	MGI:5638539
ht3	Slc12a5^tm1Hsav/Slc12a5^tm2Hsav	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:5638537

Genotype
MGI:5638536

hm1

• Allelic Composition: Slc12a5^tm2Hsav/Slc12a5^tm2Hsav
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

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

nervous system

abnormal dendritic spine morphology ( J:136887 )

• primary cultures of cortical neurons show longer dendritic protrusions of pyramidal-shaped neurons than in wild-type cultures, with varied morphology from filopodia-like structures to protrusions with clear bulbous heads

abnormal synapse morphology ( J:136887 )

• the number of functional dendritic synapses is lower in neurons

abnormal miniature excitatory postsynaptic currents ( J:136887 )

• lower frequency of miniature excitatory postsynaptic currents (mEPSCs) in neurons but no difference in amplitude

Genotype
MGI:5638539

ht2

• Allelic Composition: Slc12a5^tm1Hsav/Slc12a5^tm2Hsav
• Genetic Background: involves: 129S1/Sv * 129S2/SvPasHsd * 129X1/SvJ * C57BL/6J * C57BL/6JOlaHsd

growth/size/body

decreased body weight ( J:101079 )

• mice exhibit normal weight at birth, however, by 2 weeks of age, they weigh about 20% less than wild-type mice and this lower weight persists until at least 7 months of age

behavior/neurological

increased susceptibility to pharmacologically induced seizures ( J:101079 )

• mutants are hypersensitive to PTZ-induced seizures, showing increased latency to clonic seizures, longer seizure duration, and shorter latency to lethality

• however, mice do not develop spontaneous seizures

abnormal habituation ( J:101079 )

• rearing activity of mutants did not habituate in the open field as in controls which show more rearings at the beginning than the end of the test session

impaired spatial learning ( J:101079 )

• in the water maze, mice show a longer cumulative distance to target than controls during the learning period

• in a subsequent transfer test, mutants swim further from the target than wild-type mice

• reversal learning shows decreased ability to locate the platform

• in the second transfer test after reversal learning, mutants are closer to the previous platform location and further away from the new place than the wild-type mice

• however, mutants are able to learn the simple visually cued escape from the water maze

increased anxiety-related response ( J:101079 )

• in the elevated plus-maze, mice avoid entering the open arms almost completely, make less exploratory rearings and head dippings, and defecate more often than wild-type littermates

• although mice show normal exploration in the light-dark test, they show less rearings and defecate more frequently than wild-type mice

hyporesponsive to tactile stimuli ( J:101079 )

• mice are hyposensitive to tactile stimulation, with a lower percentage of mutants responding to a given stimulus force with calibrated von Frey hairs

decreased vertical activity ( J:101079 )

• mice show less rearings during the elevated plus-maze, in the light-dark exploration test, and in the Y-maze test

• mice however, exhibit normal spontaneous locomotor activity and motor coordination in the open field, Y-maze, rotarod, and beam tests

increased thermal nociceptive threshold ( J:101079 )

• mice are hyposensitive to thermal stimulation, showing decreased sensitivity to lower temperatures in the tail withdrawal and hot-plate tests

nervous system

nervous system phenotype ( J:101079 )

N • mice do not show gross changes in brain histology

increased susceptibility to pharmacologically induced seizures ( J:101079 )

• mutants are hypersensitive to PTZ-induced seizures, showing increased latency to clonic seizures, longer seizure duration, and shorter latency to lethality

• however, mice do not develop spontaneous seizures

reproductive system

reproductive system phenotype ( J:101079 )

N • mice are fertile

Genotype
MGI:5638537

ht3

• Allelic Composition: Slc12a5^tm1Hsav/Slc12a5^tm2Hsav
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

nervous system

abnormal dendritic spine morphology ( J:136887 )

• dendritic protrusions are longer in neurons, however, no difference is protrusion density is seen