title: Generation and characterisation of keratin 7 (K7) knockout mice.
abstract: Keratin 7 (K7) is a Type II member of the keratin superfamily and despite its widespread expression in different types of simple and transitional epithelia, its functional role in vivo remains elusive, in part due to the lack of any appropriate mouse models or any human diseases that are associated with KRT7 gene mutations. Using conventional gene targeting in mouse embryonic stem cells, we report here the generation and characterisation of the first K7 knockout mouse. Loss of K7 led to increased proliferation of the bladder urothelium although this was not associated with hyperplasia. K18, a presumptive type I assembly partner for K7, showed reduced expression in the bladder whereas K20, a marker of the terminally differentiated superficial urothelial cells was transcriptionally up-regulated. No other epithelia were seen to be adversely affected by the loss of K7 and western blot and immunofluorescence microscopy analysis revealed that the expression of K8, K18, K19 and K20 were not altered in the absence of K7, with the exception of the kidney where there was reduced K18 expression.
authors.affiliation: Centre for Dermatology & Genetic Medicine, Division of Molecular Medicine, College of Life Sciences, Dentistry & Nursing, University of Dundee, Dundee, United Kingdom. a.sandilands@dundee.ac.uk
authors.forename: Aileen
authors.initials: A
authors.lastname: Sandilands
authors.forename: Frances J D
authors.initials: FJ
authors.lastname: Smith
authors.forename: Declan P
authors.initials: DP
authors.lastname: Lunny
authors.forename: Linda E
authors.initials: LE
authors.lastname: Campbell
authors.forename: Kirsty M
authors.initials: KM
authors.lastname: Davidson
authors.forename: Stephanie F
authors.initials: SF
authors.lastname: MacCallum
authors.forename: Laura D
authors.initials: LD
authors.lastname: Corden
authors.forename: Lesley
authors.initials: L
authors.lastname: Christie
authors.forename: Stewart
authors.initials: S
authors.lastname: Fleming
authors.forename: E Birgitte
authors.initials: EB
authors.lastname: Lane
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005260:Female; D018703:Founder Effect; D005786:Gene Expression Regulation; D053538:Keratin-18 / Q000235:genetics / Q000378:metabolism; D053539:Keratin-19 / Q000235:genetics / Q000378:metabolism; D053554:Keratin-20 / Q000235:genetics / Q000378:metabolism; D053552:Keratin-7 / Q000172:deficiency / Q000235:genetics*; D053533:Keratin-8 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D001743:Urinary Bladder / Q000166:cytology / Q000378:metabolism*; D019459:Urothelium / Q000166:cytology / Q000378:metabolism*
chemical_list: D053538:Keratin-18; D053539:Keratin-19; D053554:Keratin-20; D053552:Keratin-7; D053533:Keratin-8; C489975:Krt20 protein, mouse; C507496:Krt7 protein, mouse; C486595:Krt8 protein, mouse