Mouse Genome Informatics
hm1
    Cm/Cm
involves: 101/H * C3H/He * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• death occurs at approximately E10.5 from widespread hemorrhages due to vascular defects

cardiovascular system
• at E10.5, all homozygous embryos are hemorrhagic


Mouse Genome Informatics
hm2
    Cm/Cm
involves: 101/H * C3H/HeH
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• homozygotes are not viable


Mouse Genome Informatics
hm3
    Cm/Cm
Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• homozygotes likely die before day 6 in pregnancy


Mouse Genome Informatics
ht4
    Cm/+
C3Sn.Cg-Cm/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Inner ear defects in Cm/+ mice

behavior/neurological
N
• assessments from 2 to 20 days of age found normal results in the following behavioral tests: crossed extensor reflex, forelimb/hindlimb placing, rooting reflex, negative geotaxis, grasp reflex, vibrissa placing, and eye opening (J:30380)
• the hyperactivity can be diminished by treatment with d-amphetamine, but methylphenidate increases the hyperactivity
• amphetamine-treated mice exhibit a reduction in locomotor activity unlike similarly treated wild-type mice
• heterozygous have a developmental delay in learning to right themselves, righting themselves more slowly at 5 through 9 days of age but righting themselves comparably with wild-type controls from 11 through 13 days of age
• from 13 to 20 days of age pups supported their weight for a significantly shorter time in the bar holding task
• the hyperactivity can be diminished by treatment with d-amphetamine, but methylphenidate increases the hyperactivity (J:32588)
• all heterozygotes are much more active than wild-type controls and this hyperactivity can be reduced by subcutateous or intracerebroventricular injection of the neurotoxin DSP-4, which depletes norepinephrine (J:150776)
• mice exhibit hyperactivity compared with wild-type mice (J:156905)
• however, treatment with amphetamine reduces locomotor activity (J:156905)
• by 11 days of age in increased reactivity to touch is found, with this exaggerated responsiveness increasing at 14 days of age and decreasing at 20 days of age
• first observed in a minority of heterozygotes at 11 days of age, in half of the pups by 14 days of age, and in all adults

nervous system
• in the basal and middle regions of the cochleas, occasional short regions of only two rows of outer hair cells are present instead of the normal 3
• extra hair cells in the inner hair cell row are seen in the base and apex
• the very apical 10-35% of the cochlea, show an increase in outer hair cell rows, having 4-5 rows instead of the normal 3
• extracellular dopamine levels are increased more than 80% compared to in wild-type mice
• however, dopamine extraction fraction is normal
• brain slices treated with potassium chloride in the presence of calcium give a 35% increase in norepinephrine release from the striatum and nucleus accumbens compared with wild type controls

hearing/vestibular/ear
• in the basal and middle regions of the cochleas, occasional short regions of only two rows of outer hair cells are present instead of the normal 3
• extra hair cells in the inner hair cell row are seen in the base and apex
• the very apical 10-35% of the cochlea, show an increase in outer hair cell rows, having 4-5 rows instead of the normal 3
• anterior and posterior canal truncations near the ampullae, however the lateral canal is normal, and the respective ampullae are small or absent
• when the ampulla is present, the canal is still truncated

vision/eye
• iris colobomas
• in 27% of heterozygotes one eye fails to open

growth/size
• although the body weight of heterozygotes is comparable to wild-type siblings until 7 days of age, from 7 days of age on they weigh less

homeostasis/metabolism
• extracellular dopamine levels are increased more than 80% compared to in wild-type mice
• however, dopamine extraction fraction is normal

Mouse Models of Human Disease
OMIM IDRef(s)
Attention Deficit-Hyperactivity Disorder; ADHD 143465 J:1371


Mouse Genome Informatics
ht5
    Cm/+
involves: 101/H * C3H/He * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• abnormalities are similar to Jag1tm1Grid heterozygous mice


Mouse Genome Informatics
ht6
    Cm/+
involves: 101/H * C3H/HeH
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• heterozygotes display an abnormal postural reaction
• heterozygotes are extremely hyperactive but maintain normal sleep/wake patterns
• heterozygotes show a >3-fold increase in nocturnal locomotor activity and occasional bursts of daytime activity associated with eating
• in some heterozygotes, locturnal locomotor activity exceeds 10 times that of control littermates
• heterozygotes show some tendency for head shaking
• heterozygotes show some tendency for circling

vision/eye
• in adults the eyeballs are rotated ventrally so that the pupil may be partly hidden by the lower lid
• at P14, heterozygotes are readily identified by their small eyes (J:1371)
• small eyes result from failure of the cornea and lens epithelium to separate during development (J:1371)
• eyes of heterozygotes appear smaller than normal at birth (J:13451)
• the ventral segment of the pigmented choroid, comprising about 25% of the whole, is absent
• heterozygous mutant eyes show a typical coloboma of the pigmented choroid in which a ventral segment (25% of the whole) is absent


Mouse Genome Informatics
ht7
    Cm/+
Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• the cornea has a grayish spot of variable size
• at 14 days of gestation some heterozygotes display an adhesion of the anterior pole of the lens with the thinned cornea, while others display an anterior plug of lens fibers perforating the cornea
• first detected at day 11.5 of gestation when lenses are not detatched from the corneal ectoderm and there is epithelial continuity
• at 18 days of gestation the developing lens can have a cone-like thickening of the anterior lens epithelium or, in a more severe case, lens fibers are found to penetrate through a hole in the cornea into the conjunctival sac
• eyes of newborn heterozygotes are always smaller than normal and a coloboma is visible through the transparent eyelid
• eyelids may remain closed in adults or may be opened slightly, and the pupil is often partly hidden behind the lower eyelid

behavior/neurological

nervous system
N
• population excitatory postsynaptic potential and afferent-evoked population spikes in the hippocampus are normal (J:40705)
• although the EEG activity from the hilar region of the dentate gyrus of halothan anesthetized hemizygotes is normal, tail-pinch induced theta rhythm is significantly reduced in these same mice relative to wild-type
• long-term potentiation in the hippocampal dentate gyrus is significantly attenuated
• posttetanic potentiation in the hippocampal dentate gyrus is significantly attentuated
• dentate population spikes show inhibition of paired-pulse response

integument
• the coat has a slightly abnormal texture, not as smooth as wildtype


Mouse Genome Informatics
cx8
    Jag1tm1Grid/Cm
involves: 101/H * 129S1/Sv * C3H/He * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system

nervous system


Mouse Genome Informatics
cx9
    Cm/+
Drd3tm1Stl/Drd3tm1Stl

involves: 101/H * 129S2/SvPas * C3H/HeH * C3H/HeSn * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• amphetamine-treated mice fail to exhibit a change in locomotor activity unlike similarly treated wild-type mice or Cm heterozygotes


Mouse Genome Informatics
cx10
    Cm/+
Drd2tm1Low/Drd2tm1Low

involves: 101/H * 129S2/SvPas * C3H/HeH * C3H/HeSn * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• amphetamine-treated mice exhibit a normal increase in locomotor activity (J:156905)
• locomotor activity is normal compared with wild-type mice (J:156905)
• mice exhibit reduced activity compared with Cm heterozygotes
• however, locomotor activity is normal compared with wild-type mice

nervous system
N
• extracellular dopamine levels are normal compared with wild-type mice (J:156905)
• extracellular dopamine levels are reduced compared to in Cm heterozygotes
• however, extracellular dopamine levels are normal compared with wild-type mice

homeostasis/metabolism
• extracellular dopamine levels are reduced compared to in Cm heterozygotes
• however, extracellular dopamine levels are normal compared with wild-type mice


Mouse Genome Informatics
cx11
    Cm/+
Tg(Snap25)40Micw/Tg(Snap25)40Micw

involves: C3H/HeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• the hyperactivity and suppressive effect of amphetamines found in the Cm/+ mice is rescued by homozygous expression of this transgene (J:32588)
• tail-pinched induced theta wave in halothane anesthetized mice is normal, unlike that of Cm/+ mice without the transgene (J:58598)
• paired pulse inhibition is normal and amphetamine treatment does not increase paired-pulse inhibition as it does in Cm/+ mice without the transgene (J:58598)
• despite homozygous expression of this transgene, these mice still display the head bobbing phenotype of Cm/+

vision/eye
• sunken, closed eyes characteristic of Cm/+ mice are still found despite the homozygous presence of this transgene


Mouse Genome Informatics
cx12
    Cm/+
Tg(Snap25)40Micw/0

involves: C3H/HeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• while these mice display hyperactivity, it is decreased relative to Cm/+ mice without the transgene