Mouse Genome Informatics
hm1
    Slc6a4tm1Kpl/Slc6a4tm1Kpl
B6.129-Slc6a4tm1Kpl
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• showed exaggerated immobility in response to repeated, but not acute, exposure to the tail suspension test
• traveled a significantly shorter distance in the open field
• spent significantly less time in the center of the open field
• buried significantly fewer marbles than control
• male mutant mice spend more time in an empty cage than in a cage with a strange mouse in the sociability choice test; female mutant mice did not behave differently than controls

Mouse Models of Human Disease
OMIM IDRef(s)
Autism 209850 J:192363


Mouse Genome Informatics
hm2
    Slc6a4tm1Kpl/Slc6a4tm1Kpl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• whole blood 5-HT levels are reduced

cardiovascular system
• in valvular regions, show leaflet thickening and marked collagen accumulation at the attachment site and in the leaflet itself
• these lesions are homogeneously distributed in the mitral, tricuspid, aortic, and pulmonary valves
• several areas of chondroid metaplasia are seen within the valvular tissue
• leaflet thickening in valvular regions
• develop cardiac fibrosis, with significantly more collagen in myocardial and valvular regions
• increased left ventricular lumen diameter and myocardial hypokinesis (decreased fractional shortening)
• decreased fractional shortening

muscle
• increased left ventricular lumen diameter and myocardial hypokinesis (decreased fractional shortening)
• decreased fractional shortening


Mouse Genome Informatics
hm3
    Slc6a4tm1Kpl/Slc6a4tm1Kpl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• cocaine-conditioned place preference is significantly enhanced compared to wild-type mice
• no thermal hyperalgesia is seen after unilateral chronic constrictive sciatic nerve injury unlike in wild-type mice
• increased REM sleep bouts, more bouts of short duration, and less wake time are seen in mutants compared to wild-type mice

cardiovascular system
• hypoxia-induced thickening of the distal pulmonary vessels is reduced in mutants compared to wild-type mice
• left ventricular weight/body weight is lower in mutants
• after 5 weeks under hypoxic conditions right ventricular/left ventricular + septum weight is not increased in mutants unlike in wild-type mice
• right ventricular hypertrophy is less severe after prolonged hypoxia (2-5 weeks) compared to wild-type mice
• a greater increase in right ventricular systolic pressure is seen after 5 minutes under hypoxic conditions less than 8% O2) in mutants compared to wild-type mice
• however prolonged hypoxia (2-5 weeks) produces a smaller increase in right ventricular systolic pressure compared to wild-type

nervous system
• the number of apoptotic cells in the brain is significantly decreased in neonatal mutants

homeostasis/metabolism
• whole blood serotonin levels are also significantly decreased

integument
• no thermal hyperalgesia is seen after unilateral chronic constrictive sciatic nerve injury unlike in wild-type mice


Mouse Genome Informatics
hm4
    Slc6a4tm1Kpl/Slc6a4tm1Kpl
involves: 129S1/Sv * 129X1/SvJ * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• no hypothermia in response to 8-hydroxy-2-(di-n-propylamino)tetraline treatment is seen unlike in wild-type mice
• a 60-80% decrease in serotonin levels in the brain stem, frontal cortex, hippocampus, and striatum is seen

behavior/neurological
• (+)3,4-methylenedioxymethamphetamine (MDMA) does not induce hyperactivity but instead results in hypoactivity 10 and 30 minutes after treatment


Mouse Genome Informatics
ht5
    Slc6a4tm1Kpl/Slc6a4+
B6.129-Slc6a4tm1Kpl
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• 8 week old females show a trend towards decreased preference for interacting with a stimulus mouse in a social approach assay, however this does not reach significance
• while 8 week old males do not show a change in preference for social interaction for the first trial, upon reexposure to the same social target in trial 2, males do not show attenuation of preference for social investigation between the first and second trials as seen in wild-type mice, indicating impaired social recognition in male

nervous system

growth/size


Mouse Genome Informatics
ht6
    Slc6a4tm1Kpl/Slc6a4+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• the barrel septa in layer IV of the somatosensory cortex are enlarged

behavior/neurological
• cocaine-conditioned place preference is significantly enhanced compared to wild-type mice


Mouse Genome Informatics
ht7
    Slc6a4tm1Kpl/Slc6a4+
involves: 129S1/Sv * 129X1/SvJ * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• cumulative (+)3,4-methylenedioxymethamphetamine (MDMA) induced hyperactivity is reduced by about 50% compared to wild-type


Mouse Genome Informatics
cx8
    Ptentm1Rps/Pten+
Slc6a4tm1Kpl/Slc6a4+

B6.129-Slc6a4tm1Kpl Ptentm1Rps
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• 8 week old females show a significant decrease in preference for interacting with a stimulus mouse in a social approach assay, with mice spending significantly less time interacting with the stimulus mouse than in wild-type mice or either single heterozygote, indicating impaired social approach behavior in females
• while 8 week old males do not show a change in preference for social interaction for the first trial, upon reexposure to the same social target in trial 2, males do not show attenuation of preference for social investigation between the first and second trials as seen in wild-type mice, indicating impaired social recognition in males

nervous system
• deficits in prepulse inhibition of the acoustic startle response indicate impaired sensorimotor gating
• mice show deficits in prepulse inhibition of the acoustic startle response to a similar level as single Pten heterozygotes
• however, mice respond to the olfactory-habituation-dishabituation test normally, indicating normal olfactory function

growth/size
• macrocephaly that is more severe than in either single heterozygote

Mouse Models of Human Disease
OMIM IDRef(s)
Autism 209850 J:144937


Mouse Genome Informatics
cx9
    Slc6a3tm1Mca/Slc6a3tm1Mca
Slc6a4tm1Kpl/Slc6a4tm1Kpl

involves: 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• movement in a novel environment is increased compared to wild-type and Slc6a3tm1Mca homozygotes
• double homozygotes do not display any cocaine place preference

endocrine/exocrine glands
• abnormal central anterior pituitaries with fewer acidophilic cells are seen similar to Slc6a3tm1Mca homozygotes
• small pituitary glands are seen similar to Slc6a3tm1Mca homozygotes

growth/size
• double homozygotes grow slower than wild-type but not as slowly as Slc6a3tm1Mca homozygotes

nervous system
• abnormal central anterior pituitaries with fewer acidophilic cells are seen similar to Slc6a3tm1Mca homozygotes
• small pituitary glands are seen similar to Slc6a3tm1Mca homozygotes


Mouse Genome Informatics
cx10
    Slc6a3tm1Mca/Slc6a3tm1Mca
Slc6a4tm1Kpl/Slc6a4+

involves: 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• mutants do not display any cocaine place preference


Mouse Genome Informatics
cx11
    Htr1btm1Rhn/Htr1btm1Rhn
Slc6a4tm1Kpl/Slc6a4tm1Kpl

involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• valvular fibrosis
• leaflet thickening in valvular regions
• fibrosis in myocardial and valvular regions
• increased left ventricular lumen diameter and myocardial hypokinesis (decreased fractional shortening)
• decreased fractional shortening

muscle
• increased left ventricular lumen diameter and myocardial hypokinesis (decreased fractional shortening)
• decreased fractional shortening