Phenotypes associated with this allele

• Allele Symbol: Cftr^tm1Unc
• Allele Name: targeted mutation 1, University of North Carolina
• Allele ID: MGI:1856709
• Summary: 13 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cftr^tm1Unc/Cftr^tm1Unc	B6.129P2-Cftr^tm1Unc	MGI:3689408
hm2	Cftr^tm1Unc/Cftr^tm1Unc	B6.129P2-Cftr^tm1Unc/J	MGI:2177529
hm3	Cftr^tm1Unc/Cftr^tm1Unc	involves: 129P2/OlaHsd	MGI:2177530
hm4	Cftr^tm1Unc/Cftr^tm1Unc	involves: 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:3801013
hm5	Cftr^tm1Unc/Cftr^tm1Unc	involves: 129P2/OlaHsd * C57BL/6J	MGI:3689409
ht6	Cftr^tm1Unc/Cftr^+	involves: 129P2/OlaHsd	MGI:4365832
ht7	Cftr^tm1Unc/Cftr^+	involves: BALB/cJ * C57BL/6J	MGI:3775500
cx8	Cftr^tm1Unc/Cftr^tm1Unc Tg(FABPCFTR)1Jaw/0 Tg(Scgb1a1-Scnn1b)6608Bouc/0	involves: 129P2/OlaHsd * C3H * C57BL/6 * FVB/N	MGI:5698394
cx9	Cftr^tm1Unc/Cftr^tm1Unc Tg(FABPCFTR)1Jaw/0	involves: 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:3801014
cx10	Cfmq2^129X1/SvJ/Cfmq2^129X1/SvJ Cftr^tm1Unc/Cftr^tm1Unc	involves: 129X1/SvJ * C57BL/6J	MGI:3606286
cx11	Cfmq3^129X1/SvJ/Cfmq3^C57BL/6J Cftr^tm1Unc/Cftr^tm1Unc	involves: 129X1/SvJ * C57BL/6J	MGI:3606287
cx12	Cfmq1^129X1/SvJ/Cfmq1^C57BL/6J Cftr^tm1Unc/Cftr^tm1Unc	involves: 129X1/SvJ * C57BL/6J	MGI:3606285
cx13	Cftr^tm1Unc/Cftr^+ Tmrdq1^BALB/cJ/Tmrdq1^BALB/cJ	involves: BALB/cJ * C57BL/6J	MGI:3775499

Genotype
MGI:3689408

hm1

• Allelic Composition: Cftr^tm1Unc/Cftr^tm1Unc
• Genetic Background: B6.129P2-Cftr^tm1Unc

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:44904 )

• Background Sensitivity: increased relative to homozygotes on a mixed 129P2/OlaHsd and C57BL/6J background

• Background Sensitivity: at P20 survival is 6.4% of all live births

• death usually occurs with 3 days of birth mostly from intestinal disease

digestive/alimentary system

abnormal intestine morphology ( J:44904 )

• intestinal disease involving the colon and distal ileum is a common cause of death

respiratory system

lung inflammation ( J:44904 )

• as early as P30, patchy lesions consisting of acinar dilation with interstitial thickening and accumulation of inflammatory cells and connective tissue in the alveolar walls are seen consistent with obstructive small airway disease

• this pathology becomes more severe with age

• however, no infection with any pulmonary pathogens is detected

pulmonary interstitial fibrosis ( J:44904 )

• increased deposition of collagen and other fibrillar material with age

abnormal pulmonary alveolus morphology ( J:44904 )

• as early as P30, patchy lesions consisting of acinar dilation with interstitial thickening and accumulation of inflammatory cells and connective tissue in the alveolar walls are seen consistent with obstructive small airway disease

• Background Sensitivity: at 6 months of age many alveolar surfaces are covered with a thick layer of material that is not seen in wild-type mice or in homozygotes on a mixed 129P2/OlaHsd and C57BL/6J background

abnormal bronchus morphology ( J:44904 )

• Background Sensitivity: at 6 months of age many bronchiolar surfaces are covered with a thick layer of material that is not seen in wild-type mice or in homozygotes on a mixed 129P2/OlaHsd and C57BL/6J background

• Background Sensitivity: increase in the amount of acidic mucopolysacharides in material lining the airways compared to wild-type mice and homozygotes on a mixed 129P2/OlaHsd and C57BL/6J background

• Background Sensitivity: age dependent increase in the relative proportion of non-ciliated cells in the airway epithelium with proliferation of endoplasmic reticulum and increase in the number of secretory granules in these cells; however, this increase is not seen in mice on a mixed 129P2/OlaHsd and C57BL/6J background

increased lung compliance ( J:44904 )

• Background Sensitivity: lung compliance corrected for body weight is increased compared to wild-type mice or homozygous mice on a mixed 129P2/OlaHsd and C57BL/6J background

decreased respiratory epithelial chloride transmembrane transport ( J:44904 )

• elevated negative basal nasal potential difference and absence of response to imposition of a luminally directed Cl- gradient

growth/size/body

postnatal growth retardation ( J:44904 )

• Background Sensitivity: more severe than in homozygous mice on a mixed 129P2/OlaHsd and C57BL/6J background

immune system

lung inflammation ( J:44904 )

• as early as P30, patchy lesions consisting of acinar dilation with interstitial thickening and accumulation of inflammatory cells and connective tissue in the alveolar walls are seen consistent with obstructive small airway disease

• this pathology becomes more severe with age

• however, no infection with any pulmonary pathogens is detected

Genotype
MGI:2177529

hm2

• Allelic Composition: Cftr^tm1Unc/Cftr^tm1Unc
• Genetic Background: B6.129P2-Cftr^tm1Unc/J

Pancreatic morphology and morphometry of Cftr^tm1Unc/Cftr^tm1Unc mice

cellular

impaired sperm migration in female genital tract ( J:145380 )

♂ • sperm transport within the mutant female reproductive system is significantly impaired: the average number of sperm found in mutant oviducts is only ~10% of wild-type

♂ • however, no differences in capacitation of oviductal sperm are observed

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:112450 )

• reduced ability to respond to lung infection elicited with Pseudomonas aeruginosa- laden agarose beads

postnatal lethality, incomplete penetrance ( J:32766 )

• only 8% of homozygous animals survive to 35 days of age

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:145380 )

N • although mutant FSH levels are slightly increased relative to wild-type levels, circulating levels of both FSH and LH still remain within normal range at proestrus

abnormal phospholipid level ( J:58571 )

• homozygotes exhibit a membrane lipid imbalance characterized by an increase in phospholipid-bound arachidonic acid (AA) and a decrease in phospholipid-bound docosahexaenoic acid (DHA), that is most pronounced in the pancreas, lung and ileum, organs affected in cystic fibrosis, and in the heart

• oral administration of DHA reverses the membrane lipid imbalance

digestive/alimentary system

pancreatic acinar cell zymogen granule accumulation ( J:58571 )

• zymogen granule accumulation at the apical pole of the acinar cells

dilated pancreatic acinus ( J:58571 )

• massive luminal dilatation

• oral administration of DHA reverses the pancreatic phenotype

ileum hypertrophy ( J:58571 )

• ileal hypertrophy; villus height is increased

• oral administration of DHA restores villus height to normal

intestinal obstruction ( J:112450 )

• develop intestinal blockage when fed a normal (solid) diet

decreased intestinal epithelial sodium ion transmembrane transport ( J:32766 )

• forskoliin responses in the cecum are small, variable and frequently depolarizing

respiratory system

lung inflammation ( J:58571 , J:112450 )

• homozygotes exposed to Pseudomonas LPS daily for 3 days exhibit enhanced lung inflammation, as indicated by a significant increase in neutrophil concentration compared to wild-type (J:58571)

• oral administration of DHA blocks the enhanced neutrophil infiltration in response to Pseudomonas LPS (J:58571)

• increased inflammatory response to chronic Pseudomonas aeruginosa infection (J:112450)

decreased respiratory epithelial chloride transmembrane transport ( J:112450 )

• after treatment with a chloride-depleted solution with amiloride and forskolin, the nasal potential difference (PD) was significantly different between control mice and homozygous mice

decreased respiratory epithelial sodium ion transmembrane transport ( J:112450 )

• after amiloride administration, the nasal potential difference (PD) was significantly different between control mice and homozygous mice

growth/size/body

decreased body weight ( J:145380 )

• at 6-8 and 14-16 weeks of age, total body weight is reduced by only 15% and 12%, respectively, thus not explaining the larger differences noted in average weight of reproductive organs (~50% and 36%, respectively)

postnatal growth retardation ( J:112450 )

• weighed significantly less (P 0.05) than homozygote wild-type controls at 7, 14, and 21 days of age

immune system

lung inflammation ( J:58571 , J:112450 )

• homozygotes exposed to Pseudomonas LPS daily for 3 days exhibit enhanced lung inflammation, as indicated by a significant increase in neutrophil concentration compared to wild-type (J:58571)

• oral administration of DHA blocks the enhanced neutrophil infiltration in response to Pseudomonas LPS (J:58571)

• increased inflammatory response to chronic Pseudomonas aeruginosa infection (J:112450)

increased susceptibility to bacterial infection induced morbidity/mortality ( J:112450 )

• reduced ability to respond to lung infection elicited with Pseudomonas aeruginosa- laden agarose beads

endocrine/exocrine glands

pancreatic acinar cell zymogen granule accumulation ( J:58571 )

• zymogen granule accumulation at the apical pole of the acinar cells

dilated pancreatic acinus ( J:58571 )

• massive luminal dilatation

• oral administration of DHA reverses the pancreatic phenotype

decreased corpora lutea number ( J:145380 )

♀ • female homozygotes show an average of 1.5 +/- 2.0 corpora lutea per ovary vs 9.3 +/- 1.4 in wild-type females, even though other follicle stages are present

small ovary ( J:145380 )

♀ • at 7 weeks of age, female homozygotes display smaller ovaries than wild-type females

decreased ovary weight ( J:145380 )

♀ • at 6-8 and 14-16 weeks of age, the average weight of mutant ovaries is reduced by 50% and 36%, respectively, relative to that of wild-type ovaries

♀ • however, mutant ovarian weight is restored to wild-type values after superovulation

reproductive system

impaired sperm migration in female genital tract ( J:145380 )

♂ • sperm transport within the mutant female reproductive system is significantly impaired: the average number of sperm found in mutant oviducts is only ~10% of wild-type

♂ • however, no differences in capacitation of oviductal sperm are observed

decreased corpora lutea number ( J:145380 )

♀ • female homozygotes show an average of 1.5 +/- 2.0 corpora lutea per ovary vs 9.3 +/- 1.4 in wild-type females, even though other follicle stages are present

small ovary ( J:145380 )

♀ • at 7 weeks of age, female homozygotes display smaller ovaries than wild-type females

decreased ovary weight ( J:145380 )

♀ • at 6-8 and 14-16 weeks of age, the average weight of mutant ovaries is reduced by 50% and 36%, respectively, relative to that of wild-type ovaries

♀ • however, mutant ovarian weight is restored to wild-type values after superovulation

abnormal uterine cervix morphology ( J:145380 )

♀ • only 1 of 15 female homozygotes showed cervical mucus accumulation with no other physical signs of obstruction in the uterus

small uterus ( J:145380 )

♀ • at 7 weeks of age, female homozygotes display smaller uteri than wild-type females

♀ • however, no physical signs of obstruction are observed in the uterus

decreased uterus weight ( J:145380 )

♀ • at 6-8 and 14-16 weeks of age, the average weight of mutant uteri is reduced by 56% and 36%, respectively, relative to that of wild-type uteri

♀ • however, mutant uterus weight is restored to wild-type values after superovulation

thin uterus ( J:145380 )

♀ • mutant uteri are thinner than wild-type

delayed sexual maturation ( J:145380 )

♀ • female homozygotes display a delayed onset of puberty relative to wild-type controls

decreased ovulation rate ( J:145380 )

♀ • female homozygotes display reduced oocyte ovulation rates relative to wild-type females

♀ • however, normal ovulation rates are observed after superovulation with exogenous hormone (PMSG + hCG) injections

absent estrous cycle ( J:145380 )

♀ • unlike wild-type females, 41.7% of 14-16-wk-old mutant females never enter estrus but are constantly in diestrus

prolonged estrous cycle ( J:145380 )

♀ • at 14-16 weeks of age, female homozygotes that display at least one estrous cycle show half as many cycles as wild-type females, resulting in a 2-fold increase in average cycle length

reduced female fertility ( J:145380 )

♀ • female homozygotes exhibit reduced fertility with significantly fewer numbers of litters and smaller litter sizes relative to wild-type females

♀ • 20% of female homozygotes are unable to give birth over a 5-month mating period

♀ • following induction of superovulation, only 1 of 10 mutant females that displayed vaginal plugs gave birth, but that female did give birth to 20 pups

decreased litter size ( J:145380 )

• female homozygotes show a significant decrease in average number of pups per litter relative to wild-type females (3.55 +/- 1.92 vs 6.56 +/- 2.36, respectively)

impaired fertilization ( J:145380 )

• at 48 hrs after hCG treatment, 100% of mutant oocytes remain unfertilized, whereas the majority of embryos from superovulated wild-type females are at the 2- to 4-cell stages

• however, no significant differences in in vitro fertilization rates are observed, suggesting that decreased in vivo fertilization is more likely due to inadequate fluid control in the reproductive tract, resulting in decreased sperm number in the oviduct

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cystic fibrosis		DOID:1485	OMIM:219700	J:58571 , J:112450

Genotype
MGI:2177530

hm3

• Allelic Composition: Cftr^tm1Unc/Cftr^tm1Unc
• Genetic Background: involves: 129P2/OlaHsd

mortality/aging

premature death ( J:2079 )

• surviving mutants die by 40 days of age, with most dying during the week after weaning

postnatal lethality, incomplete penetrance ( J:2079 )

• many die during the first 5 days of postnatal development

growth/size/body

abnormal nasal mucosa morphology ( J:2079 )

• glands in the nasal mucosa exhibit dilation of ducts but no acinar hyperplasia

abnormal paranasal sinus morphology ( J:2079 )

decreased body size ( J:2079 )

• remain 10-50% smaller throughout life

distended abdomen ( J:2079 )

• distended abdomen precedes death

spleen hyperplasia ( J:2079 )

• hypocellularity of the spleen is seen after the development of intestinal obstruction

digestive/alimentary system

abnormal intestine morphology ( J:2079 )

• distension of the proximal segments of the intestine is seen in mutants with severe intestinal obstruction

• observe dark fecal matter in the intestine and peritoneal cavity and perforation of the intestine

abnormal Brunner's gland morphology ( J:2079 )

• most of the Brunner's gland is destroyed and the lumens of many of the remaining ducts are distended

abnormal crypts of Lieberkuhn morphology ( J:2079 )

• severity of damage in the crypts follows a proximal to distal gradient, with mildest changes in the duodenum and most extreme changes in the ileum and colon

• dilation of crypts and formation of concretions and cast-like structures that extend the entire length of the crypts and villi, with crypts and villi almost completely destroyed in some cases

• distended crypts contain increased amounts of mucus and are even present in ileum and colon of mutants without intestinal obstructions

coiled cecum ( J:2079 )

• cecum is coiled and worm-like in appearance and the lumen is narrowed and partially or completely impacted with hard, sticky fecal pellets

abnormal colon morphology ( J:2079 )

• narrowing of the colon is seen in mutants with severe intestinal obstruction

abnormal submandibular gland morphology ( J:2079 )

• submaxillary glands show varying degrees of disruption of the serous acini, however observe no dilation of ducts or presence of inspissated material in ducts

intestinal obstruction ( J:2079 )

• some mutants develop severe intestinal obstruction and meconium ileus consisting of a mixture of mucus and fecal material

• ileum is the common site of obstruction in mice dying just after weaning while the large intestine is in mice dying more than a few days after weaning

peritoneal inflammation ( J:2079 )

• develop peritonitis

endocrine/exocrine glands

abnormal gland morphology ( J:2079 )

• presence of inspissated secretions in various glands

abnormal Brunner's gland morphology ( J:2079 )

• most of the Brunner's gland is destroyed and the lumens of many of the remaining ducts are distended

abnormal crypts of Lieberkuhn morphology ( J:2079 )

• severity of damage in the crypts follows a proximal to distal gradient, with mildest changes in the duodenum and most extreme changes in the ileum and colon

• dilation of crypts and formation of concretions and cast-like structures that extend the entire length of the crypts and villi, with crypts and villi almost completely destroyed in some cases

• distended crypts contain increased amounts of mucus and are even present in ileum and colon of mutants without intestinal obstructions

abnormal submandibular gland morphology ( J:2079 )

• submaxillary glands show varying degrees of disruption of the serous acini, however observe no dilation of ducts or presence of inspissated material in ducts

abnormal trachea gland morphology ( J:2079 )

• glands in the proximal trachea exhibit dilation of the ducts

abnormal gallbladder morphology ( J:2079 )

• gallbladders are distended or ruptured, however no lesions are observed in the liver

• mutants with intestinal obstructions exhibit almost complete destruction of the gallbladder wall with some polymorphonuclear cells present

dilated gallbladder ( J:2079 )

abnormal pancreas morphology ( J:2079 )

• dramatic alterations are not observed in the pancreas, however it is often smaller and paler and 2 of 5 mutants exhibit one or two lobes that contain some enlarged acini and contain eosinophilic material

small pancreas ( J:2079 )

• often smaller

abnormal thymus involution ( J:2079 )

• mutants present with thymic involution after development of intestinal obstruction

immune system

peritoneal inflammation ( J:2079 )

• develop peritonitis

abnormal thymus involution ( J:2079 )

• mutants present with thymic involution after development of intestinal obstruction

spleen hyperplasia ( J:2079 )

• hypocellularity of the spleen is seen after the development of intestinal obstruction

liver/biliary system

abnormal gallbladder morphology ( J:2079 )

• gallbladders are distended or ruptured, however no lesions are observed in the liver

• mutants with intestinal obstructions exhibit almost complete destruction of the gallbladder wall with some polymorphonuclear cells present

dilated gallbladder ( J:2079 )

respiratory system

abnormal nasal mucosa morphology ( J:2079 )

• glands in the nasal mucosa exhibit dilation of ducts but no acinar hyperplasia

abnormal paranasal sinus morphology ( J:2079 )

increased respiratory mucosa goblet cell number ( J:2079 )

• increased numbers of goblet cells in the respiratory tract

abnormal trachea morphology ( J:2079 )

• observe squamous metaplasia in the trachea of the oldest surviving mice

abnormal trachea gland morphology ( J:2079 )

• glands in the proximal trachea exhibit dilation of the ducts

behavior/neurological

abnormal gait ( J:2079 )

• awkward gait precedes death

hematopoietic system

abnormal thymus involution ( J:2079 )

• mutants present with thymic involution after development of intestinal obstruction

spleen hyperplasia ( J:2079 )

• hypocellularity of the spleen is seen after the development of intestinal obstruction

reproductive system

female infertility ( J:2079 )

♀ • a successful mating of one female that survived to maturity did not result in pregnancy, possibly indicating infertility, however males exhibit no abnormalities of reproductive organs

craniofacial

abnormal nasal mucosa morphology ( J:2079 )

• glands in the nasal mucosa exhibit dilation of ducts but no acinar hyperplasia

abnormal paranasal sinus morphology ( J:2079 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cystic fibrosis		DOID:1485	OMIM:219700	J:2079

Genotype
MGI:3801013

hm4

• Allelic Composition: Cftr^tm1Unc/Cftr^tm1Unc
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N

mortality/aging

postnatal lethality, incomplete penetrance ( J:21934 )

• only 5% of mice survive until weaning due to complications from intestinal obstruction

digestive/alimentary system

abnormal intestinal goblet cell morphology ( J:21934 )

• goblet cell hyperplasia occurs throughout the intestinal tract from ileum to the colon

dilated crypt of Lieberkuhn ( J:21934 )

• crypts are dilated with mucus

coiled cecum ( J:21934 )

• the cecum has a coiled "worm-like" structure

decreased intestinal epithelial chloride transmembrane transport ( J:21934 )

• cyclic-AMP stimulated transport of Cl^- ions does not occur in the intestinal epithelium

endocrine/exocrine glands

dilated crypt of Lieberkuhn ( J:21934 )

• crypts are dilated with mucus

cellular

abnormal intestinal goblet cell morphology ( J:21934 )

• goblet cell hyperplasia occurs throughout the intestinal tract from ileum to the colon

Genotype
MGI:3689409

hm5

• Allelic Composition: Cftr^tm1Unc/Cftr^tm1Unc
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

mortality/aging

postnatal lethality, incomplete penetrance ( J:44904 )

• Background Sensitivity: reduced relative to homozygotes on a congenic C57BL/6J background

• at P20 survival is 15.5% of all live births

respiratory system

respiratory system phenotype ( J:44904 )

N • Background Sensitivity: at 6 months of age bronchiolar and alveolar surfaces appear similar to wild-type as does the amount of acidic mucopolysacharides in material lining the airways and the proportion of non-ciliated cells in the broncheolar epithlium, unlike in homozygotes on a congenic C57BL/6J background

N • lung compliance corrected for body weight is similar to wild-type

abnormal vital capacity ( J:44904 )

• forced vital capacity per kg body weight is reduced compared to wild-type mice

decreased respiratory epithelial chloride transmembrane transport ( J:44904 )

• elevated negative basal nasal potential difference and absence of response to imposition of a luminally directed Cl- gradient

growth/size/body

postnatal growth retardation ( J:44904 )

• Background Sensitivity: less severe than in homozygous mice on a congenic C57BL/6J background

Genotype
MGI:4365832

ht6

• Allelic Composition: Cftr^tm1Unc/Cftr⁺
• Genetic Background: involves: 129P2/OlaHsd

reproductive system

asthenozoospermia ( J:122297 )

♂ • male heterozygotes show a significant reduction in sperm motility with compromised forward movement parameters relative to wild-type controls

impaired sperm capacitation ( J:122297 )

♂ • after 2-hr incubation in capacitation-inducing medium, the % of capacitated sperm (B pattern) in male heterozygotes is significantly lower than that of wild-type controls, as shown by CTC staining

♂ • reduced sperm capacitation is associated with defective HCO₃^_ transport, including a reduction in the magnitude of HCO₃^_ -induced membrane hyperpolarization and a decrease in HCO₃^_ -induced cAMP production relative to wild-type controls

decreased litter size ( J:122297 )

• when crossed to wild-type females, male heterozygotes yield a reduced litter size relative to wild-type males (on average 4.20 +/- 1.09 vs 6.22 +/- 0.67, respectively)

reduced male fertility ( J:122297 )

♂ • only 5 of 9 male heterozygotes mated with wild-type females produce offspring

impaired fertilization ( J:122297 )

• in vitro fertilizing capacity of heterozygous mutant sperm is significantly lower than that of wild-type sperm (16% vs 48.5%, respectively)

• in addition, heterozygous mutant sperm show reduced binding and penetration of zona pellucida-free eggs relative to wild-type sperm

cellular

asthenozoospermia ( J:122297 )

♂ • male heterozygotes show a significant reduction in sperm motility with compromised forward movement parameters relative to wild-type controls

Genotype
MGI:3775500

ht7

• Allelic Composition: Cftr^tm1Unc/Cftr⁺
• Genetic Background: involves: BALB/cJ * C57BL/6J

reproductive system

transmission ratio distortion ( J:125558 )

• excess BALB/cJ alleles in 3-week old non-cystic fibrosis affected females

Genotype
MGI:5698394

cx8

• Allelic Composition: Cftr^tm1Unc/Cftr^tm1Unc; Tg(FABPCFTR)1Jaw/0; Tg(Scgb1a1-Scnn1b)6608Bouc/0
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6 * FVB/N

mortality/aging

postnatal lethality, incomplete penetrance ( J:191673 )

• survival is reduced by about 70% at P3

respiratory system

respiratory system inflammation ( J:191673 )

• airway inflammation levels are similar to single Tg(Scgb1a1-Scnn1b)6608Bouc mice

pulmonary epithelial necrosis ( J:191673 )

• airway necrosis is increased compared to single Tg(Scgb1a1-Scnn1b)6608Bouc mice

abnormal mucociliary clearance ( J:191673 )

• intraluminal mucus obstruction is increased compared to single Tg(Scgb1a1-Scnn1b)6608Bouc mice

immune system

respiratory system inflammation ( J:191673 )

• airway inflammation levels are similar to single Tg(Scgb1a1-Scnn1b)6608Bouc mice

Genotype
MGI:3801014

cx9

• Allelic Composition: Cftr^tm1Unc/Cftr^tm1Unc; Tg(FABPCFTR)1Jaw/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N

respiratory system

abnormal alveolar macrophage physiology ( J:129519 )

• cAMP-induced currents CL^- in alveolar macrophages are absent in these mice

• cultured alveolar macrophages are impaired in their ability to kill bacteria that have been phagocytosed

• alveolar macrophages contain 4 times more live intracellular P. aeruginosa bacteria than controls 4 hours after infection

• defective killing of E. Coli in culture also occurs with 3 times more surviving bacteria found two hours post-infection than in controls

• lysosome acidification is defective in alveolar macrophage with pH being at least 1 unit higher than in controls

mortality/aging

mortality/aging ( J:21934 )

N • the high lethality rate of Cftr^tm1Unc homozygotes is prevented by the presence of the Tg(FABPCFTR)1Jaw transgene

digestive/alimentary system

abnormal colon goblet cell morphology ( J:21934 )

• goblet cell hyperplasia occurs in the colon

• transgene expression prevents the goblet cell hyperplasia that occurs in the small intestine of Cftr^tm1Unc homozygotes

abnormal cecum morphology ( J:21934 )

• transgene expression prevents the coiled "worm-like" structure of the cecum that occurs in Cftr^tm1Unc homozygotes

decreased intestinal epithelial chloride transmembrane transport ( J:21934 )

• cyclic-AMP stimulated transport of Cl^- ions does not occur in the large intestine

• cyclic-AMP stimulated transport of Cl^- ions that is absent in the small intestinal epithelium of Cftr^tm1Unc homozygotes is restored in these mice

endocrine/exocrine glands

abnormal colon goblet cell morphology ( J:21934 )

• goblet cell hyperplasia occurs in the colon

• transgene expression prevents the goblet cell hyperplasia that occurs in the small intestine of Cftr^tm1Unc homozygotes

cellular

abnormal colon goblet cell morphology ( J:21934 )

• goblet cell hyperplasia occurs in the colon

• transgene expression prevents the goblet cell hyperplasia that occurs in the small intestine of Cftr^tm1Unc homozygotes

Genotype
MGI:3606286

cx10

• Allelic Composition: Cfmq2^129X1/SvJ/Cfmq2^129X1/SvJ; Cftr^tm1Unc/Cftr^tm1Unc
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

mortality/aging

mortality/aging ( J:101842 )

N • increased survival

digestive/alimentary system

abnormal crypts of Lieberkuhn morphology ( J:101842 )

• decreased mucus accumulation in intestinal crypts

intestinal inflammation ( J:101842 )

• reduced instestinal inflammation

endocrine/exocrine glands

abnormal crypts of Lieberkuhn morphology ( J:101842 )

• decreased mucus accumulation in intestinal crypts

growth/size/body

decreased body weight ( J:101842 )

• closer to normal body weight

immune system

intestinal inflammation ( J:101842 )

• reduced instestinal inflammation

Genotype
MGI:3606287

cx11

• Allelic Composition: Cfmq3^129X1/SvJ/Cfmq3^C57BL/6J; Cftr^tm1Unc/Cftr^tm1Unc
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

mortality/aging

mortality/aging ( J:101842 )

N • increased survival

digestive/alimentary system

abnormal crypts of Lieberkuhn morphology ( J:101842 )

• decreased mucus accumulation in intestinal crypts

intestinal inflammation ( J:101842 )

• reduced instestinal inflammation

endocrine/exocrine glands

abnormal crypts of Lieberkuhn morphology ( J:101842 )

• decreased mucus accumulation in intestinal crypts

growth/size/body

decreased body weight ( J:101842 )

• closer to normal body weight

immune system

intestinal inflammation ( J:101842 )

• reduced instestinal inflammation

Genotype
MGI:3606285

cx12

• Allelic Composition: Cfmq1^129X1/SvJ/Cfmq1^C57BL/6J; Cftr^tm1Unc/Cftr^tm1Unc
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

mortality/aging

mortality/aging ( J:101842 )

N • increased survival

digestive/alimentary system

abnormal crypts of Lieberkuhn morphology ( J:101842 )

• decreased mucus accumulation in intestinal crypts

intestinal inflammation ( J:101842 )

• reduced instestinal inflammation

immune system

intestinal inflammation ( J:101842 )

• reduced instestinal inflammation

growth/size/body

decreased body weight ( J:101842 )

• closer to normal body weight

endocrine/exocrine glands

abnormal crypts of Lieberkuhn morphology ( J:101842 )

• decreased mucus accumulation in intestinal crypts

Genotype
MGI:3775499

cx13

• Allelic Composition: Cftr^tm1Unc/Cftr⁺; Tmrdq1^BALB/cJ/Tmrdq1^BALB/cJ
• Genetic Background: involves: BALB/cJ * C57BL/6J

reproductive system

transmission ratio distortion ( J:125558 )

♀ • excess BALB/cJ alleles in 3-week old non-cystic fibrosis affected females