Phenotypes associated with this allele

• Allele Symbol: Ednrb^tm1Ywa
• Allele Name: targeted mutation 1, Masashi Yanagisawa
• Allele ID: MGI:1857161
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ednrb^tm1Ywa/Ednrb^tm1Ywa	B6;129-Ednrb^tm1Ywa/J	MGI:5617944
hm2	Ednrb^tm1Ywa/Ednrb^tm1Ywa	involves: 129S5/SvEvBrd	MGI:2174949
ht3	Ednrb^tm1Ywa/Ednrb^+	involves: 129S/SvEvBrd	MGI:3717430
ht4	Ednrb^tm1Ywa/Ednrb^s	involves: 129S/SvEv	MGI:3717431
cx5	Ednra^tm1Ywa/Ednra^tm1Ywa Ednrb^tm1Ywa/Ednrb^tm1Ywa	involves: 129S7/SvEvBrd	MGI:3036213
cx6	Ednrb^tm1Ywa/Ednrb^+ Tg(Mt1-RET)304Ina/0	involves: 129S7/SvEvBrd * BALB/c * C57BL/6	MGI:5303093

Genotype
MGI:5617944

hm1

• Allelic Composition: Ednrb^tm1Ywa/Ednrb^tm1Ywa
• Genetic Background: B6;129-Ednrb^tm1Ywa/J

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

Colon crypt proliferation in Ednrb^tm1Ywa/Ednrb^tm1Ywa mice

digestive/alimentary system

decreased feces water content ( J:216833 )

• mice show reduced stool water content

abnormal intestinal mucosa morphology ( J:216833 )

• distal colon shows increased thickness of the mucosal layer

abnormal large intestine crypts of Lieberkuhn morphology ( J:216833 )

• total crypt length is increased distally in the colon at P7 and P18

• however, crypt length and proliferation in the proximal colon are not different from wild-type mice

abnormal colon goblet cell morphology ( J:216833 )

• goblet cell number and size are increased in the distal (aganglionic) colon at P18

• goblet cell number and size are decreased in the proximal colon at P18

abnormal colon morphology ( J:216833 )

• distal colon shows increased thickness of the mucosal layer

• mice show expansion of the proliferative zone in the distal colon at P7 and P18

abnormal intestine physiology ( J:216833 )

• transepithelial resistance is increased in the distal colon

• mice exhibit hindered transport of particles in intact mucus on colon epithelium indicating increased mucus viscosity in the distal colon and enhanced barrier properties

• however, chloride secretion from crypt enterocytes in the distal colon in response to stimulation with either carbachol or forskolin is similar to wild-type mice

endocrine/exocrine glands

abnormal large intestine crypts of Lieberkuhn morphology ( J:216833 )

• total crypt length is increased distally in the colon at P7 and P18

• however, crypt length and proliferation in the proximal colon are not different from wild-type mice

abnormal colon goblet cell morphology ( J:216833 )

• goblet cell number and size are increased in the distal (aganglionic) colon at P18

• goblet cell number and size are decreased in the proximal colon at P18

cellular

abnormal colon goblet cell morphology ( J:216833 )

• goblet cell number and size are increased in the distal (aganglionic) colon at P18

• goblet cell number and size are decreased in the proximal colon at P18

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:216833

Genotype
MGI:2174949

hm2

• Allelic Composition: Ednrb^tm1Ywa/Ednrb^tm1Ywa
• Genetic Background: involves: 129S5/SvEvBrd

mortality/aging

premature death ( J:22206 )

• all die prematurely with an average age at death of 25 days

growth/size/body

cachexia ( J:22206 )

• although appearing normal at birth, all become increasingly sick and emaciated from week 2 to 4

postnatal growth retardation ( J:22206 )

digestive/alimentary system

aganglionic megacolon ( J:22206 )

• gross distention of the intestine

• myenteric ganglion neurons between the longitudinal muscle layer and the inner circular smooth muscle layer are completely absent in the spastic colon

• sometimes with perforations leading to peritonitis

intestinal obstruction ( J:22206 )

• distal portion of the colon is narrow and spastic

• variable but spastic colon usually spans the entire sigmoid colon to the distal rectum (aganglionic megacolon region)

vision/eye

abnormal choroid pigmentation ( J:22206 )

• choroid layer of the retina lacks melanin but the retinal pigment epithelium is normal

immune system

decreased acute inflammation ( J:103977 )

• inflammatory response to topical application of arachidonic acid is significantly reduced (by about 65%)

• pruritic response is normal

pigmentation

abnormal coat/hair pigmentation ( J:22206 )

abnormal hair follicle melanocyte morphology ( J:22206 )

• absence of melanocytes in hair bulbs where the coat is white and normal numbers in pigmented areas

white spotting ( J:22206 )

• extensive white spotting becomes apparent by day 3-4

• 90% of the coat is white

• absence of melanin in the coat hair where the hair is white

variable depigmentation ( J:22206 )

• extensive white spotting becomes apparent by day 3-4

• 90% of the skin is unpigmented

abnormal choroid pigmentation ( J:22206 )

• choroid layer of the retina lacks melanin but the retinal pigment epithelium is normal

behavior/neurological

hypoalgesia ( J:103977 )

• algesic response to phenylbenzoquinone is absent

integument

abnormal coat/hair pigmentation ( J:22206 )

abnormal hair follicle melanocyte morphology ( J:22206 )

• absence of melanocytes in hair bulbs where the coat is white and normal numbers in pigmented areas

white spotting ( J:22206 )

• extensive white spotting becomes apparent by day 3-4

• 90% of the coat is white

• absence of melanin in the coat hair where the hair is white

variable depigmentation ( J:22206 )

• extensive white spotting becomes apparent by day 3-4

• 90% of the skin is unpigmented

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:93622
Waardenburg syndrome type 4A		DOID:0110953	OMIM:277580	J:93622

Genotype
MGI:3717430

ht3

• Allelic Composition: Ednrb^tm1Ywa/Ednrb⁺
• Genetic Background: involves: 129S/SvEvBrd

immune system

decreased acute inflammation ( J:103977 )

• inflammatory response to topical application of arachidonic acid is reduced by 37 or 51%

• pruritic response is normal

behavior/neurological

hypoalgesia ( J:103977 )

• algesic response to phenylbenzoquinone is reduced by 80%

Genotype
MGI:3717431

ht4

• Allelic Composition: Ednrb^tm1Ywa/Ednrb^s
• Genetic Background: involves: 129S/SvEv

cardiovascular system

increased mean systemic arterial blood pressure ( J:60070 )

homeostasis/metabolism

abnormal blood gas level ( J:60070 )

• increased partial CO2 pressure under conditions of hypercapnia relative to normal air pressure values

• decreased partial O2 pressure under conditions of hypoxia relative to normal air pressure values

hypercapnia ( J:60070 )

• increased partial CO2 pressure in the blood under conditions of hypercapnia relative to normal air pressure values

hypoxia ( J:60070 )

• decreased partial O2 pressure in the blood under conditions of hypoxia relative to normal air pressure values

Genotype
MGI:3036213

cx5

• Allelic Composition: Ednra^tm1Ywa/Ednra^tm1Ywa; Ednrb^tm1Ywa/Ednrb^tm1Ywa
• Genetic Background: involves: 129S7/SvEvBrd

mortality/aging

prenatal lethality ( J:46640 )

• these double mutants highly resemble Ece1^tm1Reh

cardiovascular system

abnormal artery morphology ( J:46640 )

• the peripheral vessels are dilated

pericardial effusion ( J:46640 )

• along with dilation of the peripheral vasculature this is consistent with cardiac failure

homeostasis/metabolism

pericardial effusion ( J:46640 )

• along with dilation of the peripheral vasculature this is consistent with cardiac failure

Genotype
MGI:5303093

cx6

• Allelic Composition: Ednrb^tm1Ywa/Ednrb⁺; Tg(Mt1-RET)304Ina/0
• Genetic Background: involves: 129S7/SvEvBrd * BALB/c * C57BL/6

mortality/aging

decreased tumor-free survival time ( J:155735 )

• life span after tumor development is shorter than in single Tg(Mt1-RET)304Ina hemizygotes

neoplasm

increased metastatic potential ( J:155735 )

• lung metastasis after tumor development is significantly higher than in Tg(Mt1-RET)304Ina hemizygotes

increased melanoma incidence ( J:155735 )

• melanomagenesis proceeds without a pre-existing benign lesion, indicating de novo melanoma development

• location and shape of tumors is similar to those in single Tg(Mt1-RET)304Ina hemizygotes

• 68.8% of tumors less than 500 mm³ in size are malignant and the rest (31.2%) are premalignant

• 80.8% tumors from mutants are malignant and the rest are premalignant

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
melanoma		DOID:1909		J:155735