Phenotypes associated with this allele

• Allele Symbol: Nrg1^tm1Cbm
• Allele Name: targeted mutation 1, Carmen Birchmeier
• Allele ID: MGI:1928489
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nrg1^tm1Cbm/Nrg1^tm1Cbm	involves: 129P2/OlaHsd	MGI:3621550
hm2	Nrg1^tm1Cbm/Nrg1^tm1Cbm	involves: 129P2/OlaHsd * C57BL/6	MGI:2175167
ht3	Nrg1^tm1Cbm/Nrg1^+	involves: 129P2/OlaHsd	MGI:3530781
cn4	Nrg1^tm1Cbm/Nrg1^tm3Cbm Isl2^tm1Arbr/Isl2^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J	MGI:3723120
cn5	Nrg1^tm1Cbm/Nrg1^tm3Cbm Isl1^tm1(cre)Tmj/Isl1^+	involves: 129P2/OlaHsd * 129X1/SvJ	MGI:2653523
cx6	Erbb2^tm1Cbm/Erbb2^+ Erbb3^tm2Cbm/Erbb3^+ Nrg1^tm1Cbm/Nrg1^+	involves: 129P2/OlaHsd	MGI:3530779
cx7	Erbb2^tm1Cbm/Erbb2^+ Nrg1^tm1Cbm/Nrg1^+	involves: 129P2/OlaHsd	MGI:3530776

Genotype
MGI:3621550

hm1

• Allelic Composition: Nrg1^tm1Cbm/Nrg1^tm1Cbm
• Genetic Background: involves: 129P2/OlaHsd

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

nervous system

abnormal sympathetic ganglion morphology ( J:48515 )

• lack neural crest cell precursor cells in the anlage of the primary sympathetic ganglion chain

cardiovascular system

abnormal myocardium layer morphology ( J:119151 )

• marker analysis indicates that ventricular myocardial differentiation is impaired

abnormal heart ventricle morphology ( J:119151 )

• marker analysis indicates that ventricular myocardial differentiation is impaired

• however, ventricular cell proliferation is normal

embryo

abnormal neural crest cell migration ( J:48515 )

• neural crest cells are scarce at positions ventral of the neural tube and lateral of the dorsal aorta and accumulate at dorsal positions

cellular

abnormal neural crest cell migration ( J:48515 )

• neural crest cells are scarce at positions ventral of the neural tube and lateral of the dorsal aorta and accumulate at dorsal positions

muscle

abnormal myocardium layer morphology ( J:119151 )

• marker analysis indicates that ventricular myocardial differentiation is impaired

Genotype
MGI:2175167

hm2

• Allelic Composition: Nrg1^tm1Cbm/Nrg1^tm1Cbm
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:29971 )

• all mutant embryos die by E11.5

cardiovascular system

trabecula carnea hypoplasia ( J:29971 )

• however, atria were morphologically normal

failure of atrioventricular cushion closure ( J:29971 )

• at E10.5, the endocardial cusion was not closed, and the mesenchymal cells forming the cusion were reduced in number

enlarged heart ( J:29971 )

• frequently observed

enlarged pericardium ( J:29971 )

• frequently observed

irregular heartbeat ( J:29971 )

muscle

trabecula carnea hypoplasia ( J:29971 )

• however, atria were morphologically normal

nervous system

absent oligodendrocytes ( J:52282 )

• no identifiable immature oligodendrocytes were observed in spinal cord explant cultures

• addition of recombinant Nrg1 protein to the cultures rescued this phenotype

decreased radial glial cell number ( J:82745 )

• generation of radial glia is impaired

decreased Schwann cell precursor number ( J:29971 )

• Schwann cell precursors in the trunk appear reduced in number

abnormal cranial ganglia morphology ( J:29971 )

• cranial ganglia cells are reduced in number

• distinct ganglia are altered to different extents

• geniculate and vestibular-cochlea ganglia appear unaffected

• loss of neural-crest derived cells in the ganglia are thought to account for the morphological changes

small petrosal ganglion ( J:29971 )

• projections are disorganized; projections to CNS often absent

small nodose ganglion ( J:29971 )

• projections are disorganized

abnormal superior vagus ganglion morphology ( J:29971 )

• the jugular ganglion is described as abnormal

abnormal cranial nerve morphology ( J:29971 )

• cranial nerves are severely altered, whereas other peripheral projections appear normal

abnormal mandibular nerve innervation pattern ( J:29971 )

• mandibular projections and axonal connections between trigeminus and hindbrain are lost

absent trigeminal nerve ( J:29971 )

• lost, particularly the dorsal part

cellular

absent oligodendrocytes ( J:52282 )

• no identifiable immature oligodendrocytes were observed in spinal cord explant cultures

• addition of recombinant Nrg1 protein to the cultures rescued this phenotype

decreased radial glial cell number ( J:82745 )

• generation of radial glia is impaired

decreased Schwann cell precursor number ( J:29971 )

• Schwann cell precursors in the trunk appear reduced in number

growth/size/body

enlarged heart ( J:29971 )

• frequently observed

Genotype
MGI:3530781

ht3

• Allelic Composition: Nrg1^tm1Cbm/Nrg1⁺
• Genetic Background: involves: 129P2/OlaHsd

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:100313 )

• 15 days after doxorubicin treatment to induce cardiac injury, survival is significantly lower in homozygotes (15%) than wild-type (33%)

nervous system

abnormal myelination ( J:90038 )

• hypomyelination; thin myelin sheath of sciatic nerve observed at P10 and at 6 months of age

• more pronounced for large caliber axons than small caliber axons

abnormal nerve conduction ( J:90038 )

• reduced nerve conduction velocity measured in the sciatic nerve, but with normal current amplitudes and muscle compound action potentials

cardiovascular system

decreased heart weight ( J:100313 )

• 4 days after doxorubicin treatment, homozygotes show a significant decrease in heart (29% loss) and left ventricle (27% loss) weight compared to wild-type (15% for heart and 13% for left ventricle)

abnormal cardiovascular system physiology ( J:100313 )

• exhibit more severe doxorubicin-induced cardiotoxicity than wild-type, with lower left ventricular systolic pressure and left ventricular midwall fractional shortening

decreased heart left ventricle muscle contractility ( J:100313 )

• doxorubicin-induced cardiac injury causes a higher reduction in left ventricular systolic pressure than in wild-type

• doxorubicin-induced cardiac injury causes a higher reduction in left ventricular midwall fractional shortening than in wild-type

growth/size/body

weight loss ( J:100313 )

• 4 days after doxorubicin treatment, homozygotes show an increase in the loss of body weight (27%) compared to wild-type (11%)

muscle

decreased heart left ventricle muscle contractility ( J:100313 )

• doxorubicin-induced cardiac injury causes a higher reduction in left ventricular systolic pressure than in wild-type

• doxorubicin-induced cardiac injury causes a higher reduction in left ventricular midwall fractional shortening than in wild-type

homeostasis/metabolism

increased susceptibility to xenobiotic induced morbidity/mortality ( J:100313 )

• 15 days after doxorubicin treatment to induce cardiac injury, survival is significantly lower in homozygotes (15%) than wild-type (33%)

Genotype
MGI:3723120

cn4

• Allelic Composition: Nrg1^tm1Cbm/Nrg1^tm3Cbm; Isl2^tm1Arbr/Isl2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J

mortality/aging

neonatal lethality, incomplete penetrance ( J:69623 )

• ~90% of mice die at birth, with phenotype similar to Nrg1^tm1Cbm homozygous embryos

nervous system

absent Schwann cells ( J:69623 )

• Schwann cells are absent from intramuscular motor axons between E13.5-E16.5

abnormal nervous system development ( J:69623 )

abnormal motor neuron morphology ( J:69623 )

• motor neurons are defasciculated and disorganized

abnormal motor neuron innervation pattern ( J:69623 )

• in developing muscle, motor axons largely retract by birth; by E18.5, motor axons and terminals are absent

abnormal neuromuscular synapse morphology ( J:69623 )

• at diaphragm synapses, band of acetylcholine receptors (AChRs) is wider (17.5% of muscle length) than in wild-type muscle (7% of muscle length)

cellular

absent Schwann cells ( J:69623 )

• Schwann cells are absent from intramuscular motor axons between E13.5-E16.5

Genotype
MGI:2653523

cn5

• Allelic Composition: Nrg1^tm1Cbm/Nrg1^tm3Cbm; Isl1^tm1(cre)Tmj/Isl1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129X1/SvJ

muscle

abnormal muscle spindle morphology ( J:80793 )

• mutants exhibit a defect in muscle spindle differentiation in the dorsal root ganglion and motor neurons

nervous system

decreased Schwann cell number ( J:80793 )

• selective absence of Schwann cells at E16.5 in adductor and gracilis muscles but not in other muscles

abnormal muscle spindle morphology ( J:80793 )

• mutants exhibit a defect in muscle spindle differentiation in the dorsal root ganglion and motor neurons

abnormal proprioceptive neuron morphology ( J:80793 )

• parvalbumin+ proprioceptive afferents are present in E16.5 hindlimb muscles and initiate contact with individual myofibers, but they do not develop annulospiral branches around the myofibers

• parvalbumin+ proprioceptive terminals at muscle spindles remain primitive and unbranched at E18.5

• however, survival and initial differentiation of proprioceptive afferent sensory neurons is not impaired

cellular

decreased Schwann cell number ( J:80793 )

• selective absence of Schwann cells at E16.5 in adductor and gracilis muscles but not in other muscles

Genotype
MGI:3530779

cx6

• Allelic Composition: Erbb2^tm1Cbm/Erbb2⁺; Erbb3^tm2Cbm/Erbb3⁺; Nrg1^tm1Cbm/Nrg1⁺
• Genetic Background: involves: 129P2/OlaHsd

nervous system

abnormal myelination ( J:90038 )

• hypomyelination; thin myelin sheath of sciatic nerve observed at P10 and at 6 months of age

abnormal nerve conduction ( J:90038 )

• reduced nerve conduction velocity measured in the sciatic nerve, but with normal current amplitudes and muscle compound action potentials

Genotype
MGI:3530776

cx7

• Allelic Composition: Erbb2^tm1Cbm/Erbb2⁺; Nrg1^tm1Cbm/Nrg1⁺
• Genetic Background: involves: 129P2/OlaHsd

nervous system

abnormal myelination ( J:90038 )

• hypomyelination; thin myelin sheath of sciatic nerve observed at P10 and at 6 months of age

abnormal nerve conduction ( J:90038 )

• reduced nerve conduction velocity measured in the sciatic nerve, but with normal current amplitudes and muscle compound action potentials