Phenotypes associated with this allele

• Allele Symbol: Cftr^tm1Hgu
• Allele Name: targeted mutation 1, MRC Human Genetics Unit
• Allele ID: MGI:1856710
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cftr^tm1Hgu/Cftr^tm1Hgu	CF/1Ztm	MGI:3774122
hm2	Cftr^tm1Hgu/Cftr^tm1Hgu	CF/3Ztm	MGI:3774123
hm3	Cftr^tm1Hgu/Cftr^tm1Hgu	involves: 129P2/OlaHsd	MGI:3773702
hm4	Cftr^tm1Hgu/Cftr^tm1Hgu	involves: 129P2/OlaHsd * MF1	MGI:2177531

Genotype
MGI:3774122

hm1

• Allelic Composition: Cftr^tm1Hgu/Cftr^tm1Hgu
• Genetic Background: CF/1Ztm

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

Generation 27 and 28 Cftr^tm1Hgu/Cftr^tm1Hgu mice exhibit focal hypertrophy of goblet cells

mortality/aging

lethality, incomplete penetrance ( J:112752 )

• Background Sensitivity: in early generations, 8-10% die of intestinal obstruction around weaning, survival is 76% at 3 months of age for the F8-F10 generations, early deaths are still seen at F18, but by the 25th generation, no increased mortality over wild-type is seen

digestive/alimentary system

abnormal ileal goblet cell morphology ( J:112752 )

• F28 mice show focal hypertrophy of goblet cells in the ileum, but not in the jejunum

intestinal obstruction ( J:112752 )

• Background Sensitivity: 8-10% of mutants in the early generations die of intestinal obstruction at weaning, however later generations do not exhibit intestinal blockage

reproductive system

reproductive system phenotype ( J:112752 )

N • males and females are fertile

cellular

abnormal ileal goblet cell morphology ( J:112752 )

• F28 mice show focal hypertrophy of goblet cells in the ileum, but not in the jejunum

Genotype
MGI:3774123

hm2

• Allelic Composition: Cftr^tm1Hgu/Cftr^tm1Hgu
• Genetic Background: CF/3Ztm

Generation 27 and 28 Cftr^tm1Hgu/Cftr^tm1Hgu mice exhibit focal hypertrophy of goblet cells

mortality/aging

lethality, incomplete penetrance ( J:112752 )

• Background Sensitivity: in early generations, 8-10% die of intestinal obstruction around weaning, survival is 76% at 3 months of age for the F8-F10 generations, early deaths are still seen at F18, but by the 25th generation, no increased mortality over wild-type is seen

digestive/alimentary system

abnormal ileal goblet cell morphology ( J:112752 )

• F27 mice show focal hypertrophy of goblet cells in the ileum, but not in the jejunum

intestinal obstruction ( J:112752 )

• Background Sensitivity: 8-10% of mutants in the early generations die of intestinal obstruction at weaning, however later generations do not exhibit intestinal blockage

reproductive system

reproductive system phenotype ( J:112752 )

N • males and females are fertile

cellular

abnormal ileal goblet cell morphology ( J:112752 )

• F27 mice show focal hypertrophy of goblet cells in the ileum, but not in the jejunum

Genotype
MGI:3773702

hm3

• Allelic Composition: Cftr^tm1Hgu/Cftr^tm1Hgu
• Genetic Background: involves: 129P2/OlaHsd

immune system

lung inflammation ( J:24119 )

• mutants exposed to S. aureus exhibit increased lymphoid infiltrate and bronchiolitis compared to wild-type

• mutants exposed to B. cepacia exhibit much more severe bronchopneumonia and mixed inflammatory infiltrate than wild-type

increased susceptibility to bacterial infection ( J:24119 )

• mutants are unable to clear Staphylococcus aureus and Burkholderia cepacia from the lungs and develop lung disease after repeated bacterial exposure

respiratory system

respiratory system phenotype ( J:103284 )

N • under normal conditions (without bacterial exposure), no lung abnormalities are detected in homozygotes

lung inflammation ( J:24119 )

• mutants exposed to S. aureus exhibit increased lymphoid infiltrate and bronchiolitis compared to wild-type

• mutants exposed to B. cepacia exhibit much more severe bronchopneumonia and mixed inflammatory infiltrate than wild-type

abnormal lung morphology ( J:24119 )

• mutants exhibit lung disease in response to repeated bacterial exposure

• mutants exhibit increased lymphoid infiltrate, goblet cell hyperplasia, mucus retention in the airways, bronchiolitis compared to wild-type after S. aureus infection

• mutants exhibit severe bronchopneumonia and mucus retention in the major airways, goblet cell hyperplasia and metaplasia, massive mixed inflammatory infiltrate, obliteration of smaller airways, and extensive oedema compared to wild-type after B. cepacia infection

increased respiratory mucosa goblet cell number ( J:24119 )

• mutants exposed to bacteria (S. aureus and B. cepacia) exhibit increased goblet cell hyperplasia compared to wild-type

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cystic fibrosis		DOID:1485	OMIM:219700	J:24119

Genotype
MGI:2177531

hm4

• Allelic Composition: Cftr^tm1Hgu/Cftr^tm1Hgu
• Genetic Background: involves: 129P2/OlaHsd * MF1

mortality/aging

postnatal lethality, incomplete penetrance ( J:20037 )

• low incidence of lethality due to intestinal blockage; 5% die within 1 week of birth and 2% die around weaning, with 93% surviving to adulthood

digestive/alimentary system

abnormal colon morphology ( J:14614 )

• mild colon dilatation with abnormal mucus accumulation

• distension of epithelial cells, most prominent in the crypts

meconium ileus ( J:20037 )

• approximately 5% incidence of fatal meconium ileus

decreased intestinal epithelial chloride transmembrane transport ( J:14614 )

• chloride ion transport is altered as indicated by reduced rectal and colonic/caecal potential differences

respiratory system

atelectasis ( J:14614 )

• one mutant at P30 showed mild focal pulmonary atelectasis, with mucus obstruction of a small bronchus

decreased respiratory epithelial chloride transmembrane transport ( J:14614 )

• chloride ion transport in the nose is defective as indicated by an increased nasal potential difference, but no difference is seen throughout the lower airways below the larynx

• perfusion of the trachea with a low-chloride solution shows a reduction in resultant hyperpolarization

reproductive system

abnormal vas deferens morphology ( J:14614 )

♂ • one male exhibited increased mucin in the vas deferens

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cystic fibrosis		DOID:1485	OMIM:219700	J:14614