Phenotypes associated with this allele

• Allele Symbol: Cftr^tm1Eur
• Allele Name: targeted mutation 1 Erasmus University Rotterdam
• Allele ID: MGI:1857899
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cftr^tm1Eur/Cftr^tm1Eur	B6.129P2-Cftr^tm1Eur	MGI:5445420
hm2	Cftr^tm1Eur/Cftr^tm1Eur	involves: 129P2/OlaHsd * FVB/N	MGI:5445419
cx3	Cftr^tm1Eur/Cftr^tm1Eur Nherf1^tm1Ssl/Nherf1^tm1Ssl	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:3769361

Genotype
MGI:5445420

hm1

• Allelic Composition: Cftr^tm1Eur/Cftr^tm1Eur
• Genetic Background: B6.129P2-Cftr^tm1Eur

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

digestive/alimentary system

abnormal intestinal goblet cell morphology ( J:189205 )

• increase in the number of goblet cells per crypt

abnormal small intestine crypts of Lieberkuhn morphology ( J:189205 )

• ileal crypts are filled with dense mucus material and mucin is trapped in the ileal crypts of the small intestine

• the mucus of the small intestine is attached to the epithelium and is impenetrable to 2 um beads unlike in wild-type mice in which the beads sediment through the mucus and are on the epithelium

• high bicarbonate (NaHCO3) or EDTA treatment normalizes the mucus phenotype of mutants

abnormal small intestinal crypt cell physiology ( J:189205 )

• mutants secrete a denser mucus, with 2.6 times more Muc2 glycoprotein and the small intestine shows increased mucin production

endocrine/exocrine glands

abnormal small intestine crypts of Lieberkuhn morphology ( J:189205 )

• ileal crypts are filled with dense mucus material and mucin is trapped in the ileal crypts of the small intestine

• the mucus of the small intestine is attached to the epithelium and is impenetrable to 2 um beads unlike in wild-type mice in which the beads sediment through the mucus and are on the epithelium

• high bicarbonate (NaHCO3) or EDTA treatment normalizes the mucus phenotype of mutants

cellular

abnormal intestinal goblet cell morphology ( J:189205 )

• increase in the number of goblet cells per crypt

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cystic fibrosis		DOID:1485	OMIM:219700	J:189205

Genotype
MGI:5445419

hm2

• Allelic Composition: Cftr^tm1Eur/Cftr^tm1Eur
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

growth/size/body

decreased body weight ( J:28979 )

postnatal growth retardation ( J:28979 )

digestive/alimentary system

abnormal intestinal goblet cell morphology ( J:28979 )

• focal hypertrophy of goblet cells in the crypts of Lieberkuhn, predominantly seen in deep crypts

• crypts containing hypertrophic goblet cells are located in clusters

• however, the majority of the intestine appears normal

abnormal large intestine crypts of Lieberkuhn morphology ( J:28979 )

• crypts in the colon show some mucus retention and slight dilatation and have a layer of thick mucus on top of the crypts

• however, no distention of the crypts in the small intestine or complete intestinal obstruction either in the ileum or colon is seen

decreased intestinal epithelial chloride transmembrane transport ( J:28979 )

• in the ileum, the initial potential differences and equivalent short circuit currents (Ieq) are lower, indicating that cAMP-induced activation of calcium-dependent chloride channels is reduced in the ileum

• luminal hyperpolarization induced by forksolin is reduced, whereas the response to glucose addition which activates the sodium/glucose co-transporter is normal

respiratory system

decreased respiratory epithelial chloride transmembrane transport ( J:28979 )

• basal in vivo nasal potential difference is higher than in controls

• nasal potential increases in response to a large chloride gradient created by substitution of chloride by gluconate in the superfusion solution

endocrine/exocrine glands

abnormal large intestine crypts of Lieberkuhn morphology ( J:28979 )

• crypts in the colon show some mucus retention and slight dilatation and have a layer of thick mucus on top of the crypts

• however, no distention of the crypts in the small intestine or complete intestinal obstruction either in the ileum or colon is seen

liver/biliary system

abnormal gallbladder physiology ( J:28979 )

• mutants show a reduced potential difference response to forksolin in the gallbladder, indicating that cAMP-induced activation of calcium-dependent chloride channels is reduced in the gallbladder

cellular

abnormal intestinal goblet cell morphology ( J:28979 )

• focal hypertrophy of goblet cells in the crypts of Lieberkuhn, predominantly seen in deep crypts

• crypts containing hypertrophic goblet cells are located in clusters

• however, the majority of the intestine appears normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cystic fibrosis		DOID:1485	OMIM:219700	J:28979

Genotype
MGI:3769361

cx3

• Allelic Composition: Cftr^tm1Eur/Cftr^tm1Eur; Nherf1^tm1Ssl/Nherf1^tm1Ssl
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

homeostasis/metabolism

abnormal physiological response to xenobiotic ( J:128912 )

• when activated with forskolin or 8-Br-cGMP, cAMP- and cGMP-activated CFTR transepithelial short circuit currents are completely abolished