Phenotypes associated with this allele

• Allele Symbol: Erbb2^tm1Klee
• Allele Name: targeted mutation 1, Kuo-Fen Lee
• Allele ID: MGI:2387154
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Erbb2^tm1Klee/Erbb2^tm1Klee Myl2^tm1(cre)Krc/Myl2^+	involves: 129S4/SvJae	MGI:3621642
cn2	Erbb2^tm1Haus/Erbb2^tm1Klee Gfra1^tm3Jmi/Gfra1^+ Myf5^tm3(cre)Sor/Myf5^+	involves: 129S4/SvJae * 129S4/SvJaeSor * 129X1/SvJ	MGI:4456175
cn3	Erbb2^tm1Haus/Erbb2^tm1Klee Myf5^tm3(cre)Sor/Myf5^+	involves: 129S4/SvJae * C57BL/6	MGI:3843807
cn4	Erbb2^tm1Klee/Erbb2^tm1Klee Tg(Nes-cre)1Atp/0	involves: C57BL/6 * FVB/N	MGI:2654632
cn5	Erbb2^tm1Klee/Erbb2^tm1Klee Tg(Mpz-cre)1Brn/0	involves: FVB/N	MGI:3845119
cn6	Erbb2^tm1Klee/Erbb2^tm1Klee Tg(Ckmm-cre)1Lrsn/0	Not Specified	MGI:3621643

Genotype
MGI:3621642

cn1

• Allelic Composition: Erbb2^tm1Klee/Erbb2^tm1Klee; Myl2^tm1(cre)Krc/Myl2⁺
• Genetic Background: involves: 129S4/SvJae

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:76196 )

• transthoracic arotic banding results in a significant increase in mortality (70%) versus wild-type (10%)

cardiovascular system

abnormal myocardial fiber morphology ( J:76196 )

• increase in the numbers of mitochondria and vacuoles in cardiomyoctyes, however cytoskeletal ultrastructure is unchanged

abnormal heart ventricle morphology ( J:76196 )

• increase in apoptosis in the ventricles

decreased heart left ventricle septal wall thickness ( J:76196 )

• decrease in LV septal thickness

decreased heart left ventricle posterior wall thickness ( J:76196 )

• decrease in LV posterior wall thickness

dilated cardiomyopathy ( J:76196 )

• mutants display relatively normal function at 6 weeks of age and progressively acquire features of cardiomyopathy over a 6-month period

• exhibit ventricular enlargement of both the left and right cardiac chambers and a marked increase in heart:body weight ratio

decreased heart ventricle muscle contractility ( J:76196 )

• decrease in fractional shortening, velocity of circumferential fiber shortening and a reduction of the maximum first derivative of left ventricle pressure, indicating depressed myocardium contractility, however no differences in heart rate or left ventricle end-diastolic pressure

abnormal cardiac muscle relaxation ( J:76196 )

• reduction in left ventricle dP/dt min indicates impaired left ventricle relaxation

muscle

abnormal myocardial fiber morphology ( J:76196 )

• increase in the numbers of mitochondria and vacuoles in cardiomyoctyes, however cytoskeletal ultrastructure is unchanged

dilated cardiomyopathy ( J:76196 )

• mutants display relatively normal function at 6 weeks of age and progressively acquire features of cardiomyopathy over a 6-month period

• exhibit ventricular enlargement of both the left and right cardiac chambers and a marked increase in heart:body weight ratio

decreased heart ventricle muscle contractility ( J:76196 )

• decrease in fractional shortening, velocity of circumferential fiber shortening and a reduction of the maximum first derivative of left ventricle pressure, indicating depressed myocardium contractility, however no differences in heart rate or left ventricle end-diastolic pressure

abnormal cardiac muscle relaxation ( J:76196 )

• reduction in left ventricle dP/dt min indicates impaired left ventricle relaxation

Genotype
MGI:4456175

cn2

• Allelic Composition: Erbb2^tm1Haus/Erbb2^tm1Klee; Gfra1^tm3Jmi/Gfra1⁺; Myf5^tm3(cre)Sor/Myf5⁺
• Genetic Background: involves: 129S4/SvJae * 129S4/SvJaeSor * 129X1/SvJ

nervous system

abnormal cholinergic neuron morphology ( J:160727 )

• the number of cholinergic motor neurons is decreased compared to in wild-type mice

decreased motor neuron number ( J:160727 )

• the number of cholinergic motor neurons is decreased compared to in wild-type mice

• mice exhibit a reduction in small Gfra1+ motor neurons compared with wild-type mice

• loss of gamma-motor neurons is intermediate to wild-type mice and Egr3^tm1Jmi homozygotes

• mice exhibit a decrease in large diameter motor neurons compared with wild-type mice

Genotype
MGI:3843807

cn3

• Allelic Composition: Erbb2^tm1Haus/Erbb2^tm1Klee; Myf5^tm3(cre)Sor/Myf5⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

behavior/neurological

ataxia ( J:147957 )

abnormal posture ( J:147957 )

• mice show a flexed posture when inverted

abnormal gait ( J:147957 )

• mice exhibit a wide-based, ataxic gait

nervous system

abnormal muscle spindle morphology ( J:147957 )

• only rudimentary muscle spindles with a single Egr3-positive myofiber are seen in tibialis anterior muscles at P3 in contrast to spindles in controls which have multiple Egr3+ intrafusal myofibers

• on P4 muscle spindles, few mutant spindles have the complex annulospiral afferent terminal seen around the equatorial region of intrafusal myofibers in control muscle; muscle spindle afferent terminal morphology is simple compared to controls

• spindle development fails to progress beyond E18 and mature spindles do not form

decreased muscle spindle number ( J:147957 )

• in tibialis anterior (TA) muscle, muscle spindle numbers are decreased 70% from those of controls

abnormal sensory neuron innervation pattern ( J:147957 )

• innervation of muscle spindles is simpler than observed in controls, but spindle afferent projection to the ventral spinal cord shows normal pattern

abnormal excitatory postsynaptic potential ( J:147957 )

• monosynaptic inputs from muscle spindle afferent to motor neurons are functional but reduced in amplitude; EPSPs evoked by dorsal root stimulation or evoked by muscle nerve stimulation are reduced from those of controls by similar amounts (to about 22-26% of wild-type amplitudes)

muscle

abnormal muscle spindle morphology ( J:147957 )

• only rudimentary muscle spindles with a single Egr3-positive myofiber are seen in tibialis anterior muscles at P3 in contrast to spindles in controls which have multiple Egr3+ intrafusal myofibers

• on P4 muscle spindles, few mutant spindles have the complex annulospiral afferent terminal seen around the equatorial region of intrafusal myofibers in control muscle; muscle spindle afferent terminal morphology is simple compared to controls

• spindle development fails to progress beyond E18 and mature spindles do not form

decreased muscle spindle number ( J:147957 )

• in tibialis anterior (TA) muscle, muscle spindle numbers are decreased 70% from those of controls

Genotype
MGI:2654632

cn4

• Allelic Composition: Erbb2^tm1Klee/Erbb2^tm1Klee; Tg(Nes-cre)1Atp/0
• Genetic Background: involves: C57BL/6 * FVB/N

mortality/aging

premature death ( J:81239 )

• death between 3 and 8 weeks of age

digestive/alimentary system

abnormal colon morphology ( J:81239 )

• mutants exhibit a constricted distal colon and a distended proximal colon

• mutants show an increase in the number of apoptotic cells in the myenteric layer of the colon, but no difference in apoptosis in the mucosa

growth/size/body

decreased body size ( J:81239 )

• starting at 2 weeks after birth, mutants become noticeably smaller than controls

• mutants are often less than half the size of controls at time of death

postnatal growth retardation ( J:81239 )

• starting at 2 weeks after birth, mutants become noticeably smaller than controls

distended abdomen ( J:81239 )

nervous system

abnormal enteric ganglia morphology ( J:81239 )

• loss of enteric glia in the colon by 3-4 weeks of age

abnormal enteric neuron morphology ( J:81239 )

• progressive postnatal loss of enteric neurons in the colon but not the intestine, such that there is a 55% decrease in enteric neurons at P24

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Hirschsprung's disease		DOID:10487	OMIM:600156 OMIM:606874 OMIM:606875 OMIM:608462 OMIM:611644	J:81239

Genotype
MGI:3845119

cn5

• Allelic Composition: Erbb2^tm1Klee/Erbb2^tm1Klee; Tg(Mpz-cre)1Brn/0
• Genetic Background: involves: FVB/N

normal phenotype

no abnormal phenotype detected ( J:81239 )

• mutants are indistinguishable from controls and do not show loss of enteric neurons

Genotype
MGI:3621643

cn6

• Allelic Composition: Erbb2^tm1Klee/Erbb2^tm1Klee; Tg(Ckmm-cre)1Lrsn/0
• Genetic Background: Not Specified

cardiovascular system

abnormal myocardial fiber morphology ( J:76196 )

• increase in the numbers of mitochondria and vacuoles in cardiomyoctyes, however cytoskeletal ultrastructure is unchanged

abnormal heart ventricle morphology ( J:76196 )

• increase in apoptosis in the ventricles

decreased heart left ventricle septal wall thickness ( J:76196 )

• decrease in LV septal thickness

decreased heart left ventricle posterior wall thickness ( J:76196 )

• decrease in LV posterior ventricular wall thickness

dilated cardiomyopathy ( J:76196 )

• all mutants develop dilated cardiomyopathy by 6 weeks of age

• exhbiit ventricular enlargement of both the left and right cardiac chambers and a marked increase in heart:body weight ratio

decreased heart left ventricle muscle contractility ( J:76196 )

• decrease in fractional shortening, velocity of circumferential fiber shortening and a reduction of the maximum first derivative of left ventricle pressure, indicating depressed myocardium contractility, however no differences in heart rate or left ventricle end-diastolic pressure

abnormal cardiac muscle relaxation ( J:76196 )

• reduction in left ventricle dP/dt_min indicates impaired left ventricle relaxation

muscle

abnormal myocardial fiber morphology ( J:76196 )

• increase in the numbers of mitochondria and vacuoles in cardiomyoctyes, however cytoskeletal ultrastructure is unchanged

dilated cardiomyopathy ( J:76196 )

• all mutants develop dilated cardiomyopathy by 6 weeks of age

• exhbiit ventricular enlargement of both the left and right cardiac chambers and a marked increase in heart:body weight ratio

decreased heart left ventricle muscle contractility ( J:76196 )

• decrease in fractional shortening, velocity of circumferential fiber shortening and a reduction of the maximum first derivative of left ventricle pressure, indicating depressed myocardium contractility, however no differences in heart rate or left ventricle end-diastolic pressure

abnormal cardiac muscle relaxation ( J:76196 )

• reduction in left ventricle dP/dt_min indicates impaired left ventricle relaxation