title: Conditional disruption of mouse Klf5 results in defective eyelids with malformed meibomian glands, abnormal cornea and loss of conjunctival goblet cells.
abstract: Members of the Krüppel-like family of transcription factors regulate diverse developmental processes in various organs. Previously, we have demonstrated the role of Klf4 in the mouse ocular surface. Herein, we determined the role of the structurally related Klf5, using Klf5-conditional null (Klf5CN) mice derived by mating Klf5-LoxP and Le-Cre mice. Klf5 mRNA was detected as early as embryonic day 12 (E12) in the cornea, conjunctiva and eyelids, wherein its expression increased during development. Though the embryonic eye morphogenesis was unaltered in the Klf5CN mice, postnatal maturation was defective, resulting in smaller eyes with swollen eyelids that failed to separate properly. Klf5CN palpebral epidermis was hyperplastic with 7-9 layers of keratinocytes, compared with 2-3 in the wild type (WT). Klf5CN eyelid hair follicles and sebaceous glands were significantly enlarged, and the meibomian glands malformed. Klf5CN lacrimal glands displayed increased vasculature and large number of infiltrating cells. Klf5CN corneas were translucent, thicker with defective epithelial basement membrane and hypercellular stroma. Klf5CN conjunctiva lacked goblet cells, demonstrating that Klf5 is required for conjunctival goblet cell development. The number of Ki67-positive mitotic cells was more than doubled, consistent with the increased number of Klf5CN ocular surface epithelial cells. Co-ablation of Klf4 and Klf5 resulted in a more severe ocular surface phenotype compared with Klf4CN or Klf5CN, demonstrating that Klf4 and Klf5 share few if any, redundant functions. Thus, Klf5CN mice provide a useful model for investigating ocular surface pathologies involving meibomian gland dysfunction, blepharitis, corneal or conjunctival defects.
authors: Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors: Doreswamy
authors: D
authors: Kenchegowda
authors: Sudha
authors: S
authors: Swamynathan
authors: Divya
authors: D
authors: Gupta
authors: Huajing
authors: H
authors: Wan
authors: Jeffrey
authors: J
authors: Whitsett
authors: Shivalingappa K
authors: SK
authors: Swamynathan
references: Physiol Rev. 2010 Oct;90(4):1337-81
references: 20959618
references: Mol Cell Biol. 2004 Jan;24(1):245-57
references: 14673159
references: J Biol Chem. 2001 Sep 14;276(37):34355-8
references: 11443140
references: Differentiation. 2003 Apr;71(3):206-16
references: 12694203
references: Development. 2008 Aug;135(15):2563-72
references: 18599506
references: Expert Rev Mol Med. 2005 Nov 08;7(25):1-17
references: 16274491
references: Clin Exp Ophthalmol. 2005 Jun;33(3):303-16
references: 15932539
references: Differentiation. 2006 Feb;74(1):19-29
references: 16466397
references: Invest Ophthalmol Vis Sci. 2004 Dec;45(12):4327-32
references: 15557439
references: Bioessays. 2007 Jun;29(6):549-57
references: 17508399
references: Oncogene. 2002 Sep 26;21(43):6567-72
references: 12242654
references: Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1219-27
references: 15790882
references: Invest Ophthalmol Vis Sci. 2005 Feb;46(2):579-88
references: 15671285
references: Hum Genomics. 2010 Apr;4(4):263-70
references: 20511139
references: Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16795-800
references: 16275928
references: Dev Biol. 2000 Jun 1;222(1):41-54
references: 10885745
references: PLoS One. 2010 Mar 23;5(3):e9837
references: 20352127
references: Cornea. 1996 Mar;15(2):110-9
references: 8925657
references: Invest Ophthalmol Vis Sci. 2008 Aug;49(8):3360-70
references: 18469187
references: Cell Stem Cell. 2008 Nov 6;3(5):555-67
references: 18983969
references: J Biol Chem. 2009 Mar 6;284(10):6071-8
references: 19056724
references: Dev Biol. 2009 Oct 1;334(1):243-52
references: 19632219
references: J Biol Chem. 2004 Mar 26;279(13):12093-101
references: 14726538
references: Hum Mol Genet. 2005 Nov 1;14(21):3161-8
references: 16159887
references: Invest Ophthalmol Vis Sci. 2009 Sep;50(9):4155-61
references: 19387067
references: Prostate. 2003 May 1;55(2):81-8
references: 12661032
references: Invest Ophthalmol Vis Sci. 2002 Nov;43(11):3422-9
references: 12407152
references: Development. 2010 May;137(9):1573-82
references: 20388655
references: Mol Cell Biol. 2007 Jan;27(1):182-94
references: 17060454
references: J Biol Chem. 2009 Apr 3;284(14):9549-57
references: 19189969
references: Mol Vis. 2010 Jun 18;16:1132-40
references: 20664693
references: Mol Cell Biol. 2004 Feb;24(3):1324-40
references: 14729976
references: Cancer Biol Ther. 2005 Nov;4(11):1216-21
references: 16357509
references: Invest Ophthalmol Vis Sci. 2006 Feb;47(2):582-90
references: 16431954
references: J Biol Chem. 2009 Oct 9;284(41):28243-28252
references: 19684017
references: Front Biosci. 2003 May 01;8:d687-713
references: 12700042
references: Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4092-6
references: 16249485
references: Mol Cell Biol. 2008 Jun;28(12):3967-78
references: 18391014
references: Invest Ophthalmol Vis Sci. 2005 Oct;46(10):3623-30
references: 16186342
references: Invest Ophthalmol Vis Sci. 2000 Apr;41(5):1054-62
references: 10752941
references: Nat Med. 2002 Aug;8(8):856-63
references: 12101409
references: Endocrinology. 2005 Jun;146(6):2629-38
references: 15746257
references: Dev Dyn. 2006 Apr;235(4):1074-80
references: 16470615
references: Can J Ophthalmol. 2008 Apr;43(2):170-9
references: 18347619
references: Dev Biol. 2000 Sep 1;225(1):188-200
references: 10964474
references: Cell Res. 2005 Feb;15(2):92-6
references: 15740636
references: Invest Ophthalmol Vis Sci. 2004 Feb;45(2):429-40
references: 14744882
references: Invest Ophthalmol Vis Sci. 2011 Mar 28;52(3):1762-9
references: 21051695
references: Development. 2000 Jun;127(12):2563-72
references: 10821755
references: J Biol Chem. 2001 Mar 9;276(10):6897-900
references: 11152667
references: Invest Ophthalmol Vis Sci. 2000 Nov;41(12):3665-9
references: 11053261
references: J Cell Sci. 2008 Aug 15;121(Pt 16):2629-34
references: 18653541
references: Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3109-20
references: 16123409
references: Dev Dyn. 2000 Apr;217(4):421-9
references: 10767086
references: Genes Dev. 2000 Nov 1;14(21):2701-11
references: 11069887
references: Mol Vis. 2004 Nov 23;10:901-9
references: 15570219
references: Cell Metab. 2005 Jan;1(1):27-39
references: 16054042
references: J Cell Sci. 2003 Jun 1;116(Pt 11):2157-67
references: 12692153
references: Invest Ophthalmol Vis Sci. 2004 Apr;45(4):1101-8
references: 15037575