Phenotypes associated with this allele

• Allele Symbol: Cftr^tm1Hsc
• Allele Name: targeted mutation 1, Hospital for Sick Children
• Allele ID: MGI:1857545
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cftr^tm1Hsc/Cftr^tm1Hsc	involves: 129S1/Sv * 129X1/SvJ	MGI:5766739
hm2	Cftr^tm1Hsc/Cftr^tm1Hsc	involves: 129S1/Sv * 129X1/SvJ * BALB/cJ	MGI:5766740
hm3	Cftr^tm1Hsc/Cftr^tm1Hsc	involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6J * DBA/2J	MGI:5766742
hm4	Cftr^tm1Hsc/Cftr^tm1Hsc	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:5766743
hm5	Cftr^tm1Hsc/Cftr^tm1Hsc	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:2177542
hm6	Cftr^tm1Hsc/Cftr^tm1Hsc	involves: 129S1/Sv * 129X1/SvJ * DBA/2J	MGI:2177549

Genotype
MGI:5766739

hm1

• Allelic Composition: Cftr^tm1Hsc/Cftr^tm1Hsc
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

mortality/aging

postnatal lethality, complete penetrance ( J:31759 )

• Background Sensitivity: half of homozygous mice die in the first week of age, with the remainder dying between 25- 35 days of age

Genotype
MGI:5766740

hm2

• Allelic Composition: Cftr^tm1Hsc/Cftr^tm1Hsc
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/cJ

digestive/alimentary system

abnormal intestine physiology ( J:102288 )

• jejuna obtained from class III mice (those surviving past three weeks of age) exhibit a negative basal potential difference across the intestinal epithelium, although it is less negative than that observed in jejuna from control animals

• transepithelial resistance in the jejunum of CIII mice (those surviving past three weeks of age) was higher than that seen in control animals

• the chloride channel blocker NPPB inhibited the jejunal PD measured in solid diet- and liquid diet-fed control animals to a similar extent, suggesting that the jejunal epithelium of class III mice can produce chloride secretion in the absence of Cftr

• the value of the negative potential difference across the jejunal intestinal epithelium correlates with survival in class II (survive only to weaning age) and class III (survive past 6 weeks of age) mice

• the chloride channel blocker NPPB effectively inhibits transepithelial PD in both class II and class III mice

mortality/aging

postnatal lethality, incomplete penetrance ( J:31759 )

• Background Sensitivity: most homozygotes die between birth and 25 days of age (class II mice); 31% survive longer than 6 weeks of age (class III mice)

Genotype
MGI:5766742

hm3

• Allelic Composition: Cftr^tm1Hsc/Cftr^tm1Hsc
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6J * DBA/2J

mortality/aging

postnatal lethality, incomplete penetrance ( J:102288 )

• Background Sensitivity: on this mixed genetic background, most homozygotes die between birth and 25 days of age (class I and II mice); 31% survive longer than 6 weeks of age (class III mice)

digestive/alimentary system

abnormal intestine physiology ( J:102288 )

• the chloride channel blocker NPPB inhibited the jejunal PD measured in solid diet- and liquid diet-fed control animals to a similar extent, suggesting that the jejunal epithelium of class III mice can produce chloride secretion in the absence of Cftr

• the value of the negative potential difference across the jejunal intestinal epithelium correlates with survival in class II (survive only to weaning age) and class III (survive past 6 weeks of age) mice

• the chloride channel blocker NPPB effectively inhibits transepithelial PD in both class II and class III mice, suggesting that other channels can mediate transepithelial chloride transport in mutant Cftr mice

Genotype
MGI:5766743

hm4

• Allelic Composition: Cftr^tm1Hsc/Cftr^tm1Hsc
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

mortality/aging

postnatal lethality, incomplete penetrance ( J:31759 )

• Background Sensitivity: most homozygotes survive to 20 days of age with the majority dying between 20 and 35 days of age (class II mice); 25% survive longer than 6 weeks of age (class III mice)

Genotype
MGI:2177542

hm5

• Allelic Composition: Cftr^tm1Hsc/Cftr^tm1Hsc
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

digestive/alimentary system

abnormal intestinal mucosa morphology ( J:31759 )

• increased intestinal mucosal thickness in small intestine and colon

abnormal small intestine goblet cell morphology ( J:31759 )

• increase in goblet cell population in small intestine and colon

abnormal crypts of Lieberkuhn morphology ( J:31759 )

• accumulation of secreted mucus in crypt lumina

abnormal colon goblet cell morphology ( J:31759 )

• increase in goblet cell population in small intestine and colon

intestinal obstruction ( J:31759 )

• severe intestinal obstruction in class I mice (die in first week of life)

meconium ileus ( J:31759 )

• severe intestinal obstruction in class I mice by mucus containing plug

• class II mice exhibit severe intestinal obstruction by mucus containing plug, with the ileum and jejunum the major sites of mucus accumulation with obstructive accumulation

abnormal small intestinal crypt cell physiology ( J:31759 )

• absence of cAMP-induced Cl- conductance in crypt cells isolated from ileal mucosa

• the A23187 calcium ionophore elicited an calcium-dependent Cl-selective current in ileal crypt cells in contrast to control cells

• A23187 calcium ionophore elicited a greater change in anion permeability in ileal crypts than in controls in mice on this genetic background, suggesting partial compensation of ion transport abnormalities caused by absence of Cftr in class III mice that survive past 6 weeks of age

endocrine/exocrine glands

abnormal crypts of Lieberkuhn morphology ( J:31759 )

• accumulation of secreted mucus in crypt lumina

abnormal colon goblet cell morphology ( J:31759 )

• increase in goblet cell population in small intestine and colon

growth/size/body

decreased body size ( J:31759 )

• smaller than control littermates at 2-3 weeks of age compared to controls, but this difference was not seen at 8-12 weeks of age

weight loss ( J:31759 )

• animals lose weight in the days preceding death

postnatal growth retardation ( J:31759 )

• Class I mice do not gain weight after birth

mortality/aging

postnatal lethality, incomplete penetrance ( J:31759 )

• Background Sensitivity: death in the first week of life (class I mice) or by weaning (class II mice), incomplete penetrance

• Background Sensitivity: 29.7% survive past 6 weeks of age (class III mice)

respiratory system

increased respiratory epithelial sodium ion transmembrane transport ( J:31759 )

• nasal potential difference in homozygotes is greater than controls

• greater amelioride-sensitive component of nasal potential difference suggests an increased sodium ion transport capacity in nasal epithelia

cellular

abnormal colon goblet cell morphology ( J:31759 )

• increase in goblet cell population in small intestine and colon

abnormal small intestine goblet cell morphology ( J:31759 )

• increase in goblet cell population in small intestine and colon

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cystic fibrosis		DOID:1485	OMIM:219700	J:31759

Genotype
MGI:2177549

hm6

• Allelic Composition: Cftr^tm1Hsc/Cftr^tm1Hsc
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * DBA/2J

mortality/aging

preweaning lethality, complete penetrance ( J:31759 )

• Background Sensitivity: most mice die in the first week of age or prior, since homozygotes are underrepresented at genotyping age; none survive past 25 days