The "Goldilocks Effect" in Cystic Fibrosis: identification of a lung phenotype in the cftr knockout and heterozygous mouse
(2004) In BMC Genetics 5.- Abstract
- Background: Cystic Fibrosis is a pleiotropic disease in humans with primary morbidity and mortality associated with a lung disease phenotype. However, knockout in the mouse of cftr, the gene whose mutant alleles are responsible for cystic fibrosis, has previously failed to produce a readily, quantifiable lung phenotype. Results: Using measurements of pulmonary mechanics, a definitive lung phenotype was demonstrated in the cftr-/- mouse. Lungs showed decreased compliance and increased airway resistance in young animals as compared to cftr+/+ littermates. These changes were noted in animals less than 60 days old, prior to any long term inflammatory effects that might occur, and are consistent with structural differences in the cftr-/- lungs.... (More)
- Background: Cystic Fibrosis is a pleiotropic disease in humans with primary morbidity and mortality associated with a lung disease phenotype. However, knockout in the mouse of cftr, the gene whose mutant alleles are responsible for cystic fibrosis, has previously failed to produce a readily, quantifiable lung phenotype. Results: Using measurements of pulmonary mechanics, a definitive lung phenotype was demonstrated in the cftr-/- mouse. Lungs showed decreased compliance and increased airway resistance in young animals as compared to cftr+/+ littermates. These changes were noted in animals less than 60 days old, prior to any long term inflammatory effects that might occur, and are consistent with structural differences in the cftr-/- lungs. Surprisingly, the cftr+/- animals exhibited a lung phenotype distinct from either the homozygous normal or knockout genotypes. The heterozygous mice showed increased lung compliance and decreased airway resistance when compared to either homozygous phenotype, suggesting a heterozygous advantage that might explain the high frequency of this mutation in certain populations. Conclusions: In the mouse the gene dosage of cftr results in distinct differences in pulmonary mechanics of the adult. Distinct phenotypes were demonstrated in each genotype, cftr-/-, cftr +/-, and cftr+/+. These results are consistent with a developmental role for CFTR in the lung. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/270963
- author
- Cohen, JC ; Lundblad, Lennart LU ; Bates, JHT ; Levitzky, M and Larson, JE
- organization
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- in
- BMC Genetics
- volume
- 5
- publisher
- BioMed Central (BMC)
- external identifiers
-
- wos:000223188900001
- pmid:15279681
- scopus:25444507445
- pmid:15279681
- ISSN
- 1471-2156
- DOI
- 10.1186/1471-2156-5-21
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Clinical Physiology (013242300), Clinical Physiology and Nuclear Medicine Unit (013242320)
- id
- e52721f4-5050-45e1-b732-85a4201d33c7 (old id 270963)
- date added to LUP
- 2016-04-01 15:53:57
- date last changed
- 2023-09-04 08:38:46
@article{e52721f4-5050-45e1-b732-85a4201d33c7,
abstract = {{Background: Cystic Fibrosis is a pleiotropic disease in humans with primary morbidity and mortality associated with a lung disease phenotype. However, knockout in the mouse of cftr, the gene whose mutant alleles are responsible for cystic fibrosis, has previously failed to produce a readily, quantifiable lung phenotype. Results: Using measurements of pulmonary mechanics, a definitive lung phenotype was demonstrated in the cftr-/- mouse. Lungs showed decreased compliance and increased airway resistance in young animals as compared to cftr+/+ littermates. These changes were noted in animals less than 60 days old, prior to any long term inflammatory effects that might occur, and are consistent with structural differences in the cftr-/- lungs. Surprisingly, the cftr+/- animals exhibited a lung phenotype distinct from either the homozygous normal or knockout genotypes. The heterozygous mice showed increased lung compliance and decreased airway resistance when compared to either homozygous phenotype, suggesting a heterozygous advantage that might explain the high frequency of this mutation in certain populations. Conclusions: In the mouse the gene dosage of cftr results in distinct differences in pulmonary mechanics of the adult. Distinct phenotypes were demonstrated in each genotype, cftr-/-, cftr +/-, and cftr+/+. These results are consistent with a developmental role for CFTR in the lung.}},
author = {{Cohen, JC and Lundblad, Lennart and Bates, JHT and Levitzky, M and Larson, JE}},
issn = {{1471-2156}},
language = {{eng}},
publisher = {{BioMed Central (BMC)}},
series = {{BMC Genetics}},
title = {{The "Goldilocks Effect" in Cystic Fibrosis: identification of a lung phenotype in the cftr knockout and heterozygous mouse}},
url = {{http://dx.doi.org/10.1186/1471-2156-5-21}},
doi = {{10.1186/1471-2156-5-21}},
volume = {{5}},
year = {{2004}},
}