Phenotypes associated with this allele

• Allele Symbol: Ednrb^tm1.1Nrd
• Allele Name: targeted mutation 1.1, Noah Druckenbrod
• Allele ID: MGI:5804183
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ednrb^tm1.1Nrd/Ednrb^tm1.1Nrd	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5804451
ht2	Ednrb^tm1.1Nrd/Ednrb^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5804452

Genotype
MGI:5804451

hm1

• Allelic Composition: Ednrb^tm1.1Nrd/Ednrb^tm1.1Nrd
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

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

The Ednrb^tm1.1Nrd/Ednrb^tm1.1Nrd pups are smaller and have black spots due to a melanin pigmentation defect

mortality/aging

lethality at weaning, complete penetrance ( J:226561 )

• mice die at around weaning age (~21 days)

growth/size/body

decreased body size ( J:226561 )

• mice are significantly smaller than control littermates

cachexia ( J:226561 )

• mice grow progressively weaker than wild-type controls

pigmentation

abnormal coat/hair pigmentation ( J:226561 )

• P3 pups show black spots due to a melanin pigmentation defect

white spotting ( J:226561 )

• mice exhibit a white coat color with black patches as early as P3

digestive/alimentary system

megacolon ( J:226561 )

• mice exhibit megacolon due to abnormal dilation of the colon

integument

abnormal coat/hair pigmentation ( J:226561 )

• P3 pups show black spots due to a melanin pigmentation defect

white spotting ( J:226561 )

• mice exhibit a white coat color with black patches as early as P3

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:226561

Genotype
MGI:5804452

ht2

• Allelic Composition: Ednrb^tm1.1Nrd/Ednrb⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Under severe hypoxia, the relative hypoxic area in the heart is lower in Ednrb^tm1.1Nrd/Ednrb⁺ mice

homeostasis/metabolism

decreased response of heart to induced stress ( J:226561 )

♂ • under severe hypoxia (10% or 5% O₂), heterozygotes maintain a steady (and thus higher) cardiac output relative to wild-type controls where cardiac output is decreased to about half of baseline levels

♂ • heterozygotes exhibit a higher dP/dt_max/V_ed value, indicating higher cardiac contractility, at baseline as well as under all hypoxia exposures (15%, 10% or 5% O₂) relative to wild-type controls

abnormal blood pH regulation ( J:226561 )

♂ • under severe hypoxia, blood is significantly less acidic than in wild-type controls

decreased circulating lactate level ( J:226561 )

♂ • below 15% O₂ exposure, heterozygotes show only a mild (smaller) increase in blood lactate levels (1.8 +/- 0.75 mmol/L at 10%; 2.28 0.38 mmol/L at 5%) relative to wild-type controls (4.01 +/- 1.05 mmol/L at 10%; 4.92 +/- 0.33 mmol/L at 5%)

♂ • at 5% O₂ exposure, heterozygous blood lactate levels are less than half of those in wild-type controls

♂ • however, no significant differences are noted at room air or 15% O₂

hypocapnia ( J:226561 )

♂ • heterozygotes display a significantly lower partial CO₂ pressure at room air (21% O₂), but not under 15%, 10% or 5% hypoxia, relative to wild-type controls

abnormal oxygen level ( J:226561 )

♂ • under 5% O₂ exposure, heterozygotes show a significant decrease in the relative hypoxic area (%) in brain, heart, and kidney tissue relative to wild-type controls, as shown by pimonidazole staining; this difference is more significant in heart tissue

♂ • however, no significant differences are seen in the intestine or liver

cardiovascular system

increased cardiac output ( J:226561 )

♂ • in response to severe hypoxia (10% or 5% O₂), heterozygotes show no significant change in cardiac output, unlike wild-type controls where cardiac output is reduced to about half of baseline levels

♂ • however, no significant differences are observed at baseline or under mild hypoxia (21% or 15% O₂) relative to wild-type controls

increased cardiac muscle contractility ( J:226561 )

♂ • heterozygotes exhibit a higher dP/dt_max/V_ed (maximum rate of pressure change per ventricular end-diastolic volume) at baseline as well as under all subsequent hypoxia exposures (15%, 10% or 5% O₂) relative to wild-type controls

decreased response of heart to induced stress ( J:226561 )

♂ • under severe hypoxia (10% or 5% O₂), heterozygotes maintain a steady (and thus higher) cardiac output relative to wild-type controls where cardiac output is decreased to about half of baseline levels

♂ • heterozygotes exhibit a higher dP/dt_max/V_ed value, indicating higher cardiac contractility, at baseline as well as under all hypoxia exposures (15%, 10% or 5% O₂) relative to wild-type controls

increased mean systemic arterial blood pressure ( J:226561 )

♂ • in response to 30 min of severe hypoxia (5% O₂), all heterozygotes show tolerance to hypoxia-induced hypotension (defined as MAP <40 mmHg) displaying an average MAP 60.5 +/- 53 mmHg, whereas none of wild-type controls are able to maintain MAP >40 mmHg for the entire 30-min period

muscle

increased cardiac muscle contractility ( J:226561 )

♂ • heterozygotes exhibit a higher dP/dt_max/V_ed (maximum rate of pressure change per ventricular end-diastolic volume) at baseline as well as under all subsequent hypoxia exposures (15%, 10% or 5% O₂) relative to wild-type controls