Phenotypes associated with this allele

• Allele Symbol: Calca^tm1Eme
• Allele Name: targeted mutation 1, Ronald Emeson
• Allele ID: MGI:2148538
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Calca^tm1Eme/Calca^tm1Eme	involves: 129S6/SvEvTac * Black Swiss	MGI:3629804
hm2	Calca^tm1Eme/Calca^tm1Eme	involves: 129S6/SvEvTac * C57BL/6	MGI:3700059

Genotype
MGI:3629804

hm1

• Allelic Composition: Calca^tm1Eme/Calca^tm1Eme
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss

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

cardiovascular system

decreased heart rate ( J:57708 )

• adult male homozygotes show a significant decrease in exercise-induced heart rate relative to wild-type males (604.9 25 bpm vs 679.4 20.7, respectively) during a 3-min swimming period

• however, no significant differences in basal heart rate are observed

decreased systemic arterial diastolic blood pressure ( J:57708 )

• adult male homozygotes show a slight decrease in basal diastolic blood pressure relative to wild-type mice

• however, no significant differences in basal systolic pressure, basal heart rate, basal mean arterial pressure (MAP) or exercise-induced MAP are observed

• in addition, homozygotes display no significant differences in renin-angiotensin activity relative to wild-type males, as shown by an equivalent reduction of MAP in response to losartan (an AT1 receptor antagonist)

nervous system

nervous system phenotype ( J:57708 )

N • male homozygotes exhibit no significant differences in autonomic cardiovascular regulation relative to wild-type males, as shown by comparable reductions in MAP and heart rate in response to pentolinium-induced ganglionic blockade

N • male homozygotes show normal baroreceptor reflex sensitivity to phenylephrine (a peripheral vasoconstrictor), indicating normal autonomic responsiveness

N • also, homozygotes display normal development of the neuromuscular junction, with no significant changes in nicotinic receptor localization, terminal sprouting in response to denervation, developmental regulation of AChR subunit expression or synapse elimination

Genotype
MGI:3700059

hm2

• Allelic Composition: Calca^tm1Eme/Calca^tm1Eme
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

hearing/vestibular/ear

abnormal cochlear IHC afferent innervation pattern ( J:117774 )

• at 16 weeks, homozygotes display a selective reduction of sound-evoked activity in primary afferent fibers, without changes in cochlear mechanics or OHC contributions to cochlear amplification

• in homozygotes, systematic reduction of suprathreshold wave 1 amplitudes suggests changes in cochlear processes involving synaptic transmission between IHCs and the primary cochlear afferents

• no changes in the electrically evoked or sound-evoked effects of the cholinergic innervation of OHCs are observed

abnormal auditory brainstem response ( J:117774 )

• at 16 weeks of age, mutant ABR responses are systematically reduced by a constant percentage (~20-25%) at all suprathreshold sound levels relative to wild-type, as shown by amplitude reductions in all waves, without striking latency shifts

• however, homozygotes exhibit normal ABR and DPOAE thresholds across a range of test frequencies relative to wild-type mice

• in addition, homozygotes display normal medial olivocochlear (OC) function and resistance to acoustic injury, as assessed by measuring cochlear response suppression with electrical stimulation of the OC bundle, and temporary threshold shifts after brief exposure to high level sound, respectively

nervous system

abnormal cochlear IHC afferent innervation pattern ( J:117774 )

• at 16 weeks, homozygotes display a selective reduction of sound-evoked activity in primary afferent fibers, without changes in cochlear mechanics or OHC contributions to cochlear amplification

• in homozygotes, systematic reduction of suprathreshold wave 1 amplitudes suggests changes in cochlear processes involving synaptic transmission between IHCs and the primary cochlear afferents

• no changes in the electrically evoked or sound-evoked effects of the cholinergic innervation of OHCs are observed