ABCMdb

PMID: 18239192

Hilliard TN, Zhu J, Farley R, Escudero-Garcia S, Wainwright BJ, Jeffery PK, Griesenbach U, Bush A, Davies JC, Alton EW
Nasal abnormalities in cystic fibrosis mice independent of infection and inflammation.
Am J Respir Cell Mol Biol. 2008 Jul;39(1):19-25. Epub 2008 Jan 31., [PubMed]

Sentences

No. Mutations Sentence Comment

33 ABCC7 p.Gly551Asp Adult Animals Two genotypes of adult CF mice were studied: (1) CftrTgHm1G551D (mixed background [5], termed G551D, n 5 12); (2) Cftrtm1Unc-TgN(FABPCFTR) (mixed background [23], termed FABP, n 5 6). Login to comment 34 ABCC7 p.Gly551Asp Wild-type littermates (Cftr1/1, n 5 12) of G551D mice were used as controls. Login to comment 49 ABCC7 p.Gly551Asp Nasal Lavage Nasal lavage was performed on adult G551D and wild-type mice. Login to comment 54 ABCC7 p.Gly551Asp Pup and Embryo Investigation Timed mating was performed between G551D heterozygotes (C57BL/6 background). Login to comment 56 ABCC7 p.Gly551Asp After genotyping of tail tips, two 5-mm sections were cut at 50-mm intervals from six G551D and seven wild-type pup heads, and the same number of embryo heads. Login to comment 69 ABCC7 p.Gly551Asp RE (arrowed) at depth of 4,600 mm from (A) wild-type nose and (B) G551D CF nose. Login to comment 75 ABCC7 p.Gly551Asp Heads from CF mice tended to be smaller then wild-type animals; the lateral sinus in G551D mice closed at a median depth of 5,000 mm compared with wild type at 5,800 mm (P , 0.001); and 5,000 mm in FABP (P 5 0.053 versus wild type). Login to comment 77 ABCC7 p.Gly551Asp Respiratory Epithelium RE was significantly thicker in both types of CF mice (G551D 14.8 mm, FABP 14.9 mm) compared with wild-type mice (10.0 mm; P , 0.01 for both), as shown in Figure 2. Login to comment 78 ABCC7 p.Gly551Asp Mucous cell density was significantly greater in both types of CF mice (G551D 89.6 cells/mm, FABP 84.7 cells/mm) compared with wild type (54.0 cells/mm; P , 0.001 and P 5 0.001, respectively), as shown in Figure 3. Login to comment 79 ABCC7 p.Gly551Asp Collections of inflammatory cells under the RE, all with the appearance of lymphoid aggregates, were present in at least one section in 11 out of the 12 G551D mice and in 2 out of the 6 FABP mice, compared with none of the 12 wild-type mice (x2520.8, P , 0.001). Login to comment 81 ABCC7 p.Gly551Asp Olfactory Epithelium OE was significantly thinner in both types of CF mice (G551D 32.6 mm, FABP 39.0 mm) compared with wild-type (50.8 mm; P , 0.001 for both), as shown in Figure 5. Login to comment 82 ABCC7 p.Gly551Asp OE cell density was also decreased in both types of CF mice (G551D 27.4 cells/ 1,000 mm2, FABP 28.6 cells/1,000 mm2) compared with wild-type (36.4 cells/1,000 mm2; P , 0.001 and P 5 0.001, respectively), as shown in Figure 6. Login to comment 84 ABCC7 p.Gly551Asp Nasal Lavage in Adult Mice The median cell count in nasal lavage was not significantly different between G551D (5,000 cells/ml, range 0-18,000) and wild-type mice (2,000 cells/ml, 0-20000, P 5 0.11). Login to comment 87 ABCC7 p.Gly551Asp MIP-2 concentrations were not significantly different between G551D (9.8 pg/ml, 7.2-82.0) and wild-type (10.1 pg/ml, 7.3-15.5). Login to comment 89 ABCC7 p.Gly551Asp Embryo and Pup Investigation RE and OE starting points were similar between G551D and wild-type pups and embryos. Login to comment 91 ABCC7 p.Gly551Asp Mucous cells (arrowed) in RE at depth of 3,400 mm from (A) wild-type nose and (B) G551D CF nose. Login to comment 94 ABCC7 p.Gly551Asp Area of lymphoid aggregates (arrowed) on the lateral wall of the nose in a G551D CF head at a depth of 4,200 mm. H&E, scale bar 5 100 mm. Login to comment 95 ABCC7 p.Gly551Asp different between G551D and wild-type pups or embryos (combined thickness: 11.7 mm versus 14.1 mm). Login to comment 97 ABCC7 p.Gly551Asp OE was well developed in both Day 17 embryos and pups and the thickness was similar between G551D and wild-type heads (combined thickness 50.9 mm versus 52.0 mm). Login to comment 100 ABCC7 p.Gly551Asp OE (arrowed) in the dorsum of the nose of (A) a wild-type head and (B) a G551D CF head at a depth of 4,600 mm. H&E, scale bar 5 100 mm. Login to comment 102 ABCC7 p.Gly551Asp OE (arrowed) at high power in the dorsum of the nose in (A) a wild-type head and (B) a G551D CF head at a depth of 4,600 mm. H&E, scale bar 5 100 mm. Login to comment 167 ABCC7 p.Gly551Asp Acknowledgments: The authors thank Sara Escudio Garcia and Luci Somerton for managing the G551D breeding colony and for performing the tail tip genotype analysis; John Williams for the processing of the adult tissue; Yusheng Qiu for the processing of the embryo tissue; the staff of the Central Biosciences and NHLI animal facilities; Neil Madden for help with the microbiological analysis; and Abraham Jacob, Brian Faddis, and Richard Chole, Department of Otolaryngology, Washington University School of Medicine, St. Login to comment