Cytodifferentiation of the postnatal mouse stomach in normal and Huntingtin-interacting protein 1-related-deficient mice.
Huntingtin-interacting protein 1-related (Hip1r) is highly expressed in gastric parietal cells, where it participates in vesicular trafficking associated with acid secretion. Hip1r-deficient mice have a progressive remodeling of the mucosa, including apoptotic loss of parietal cells, glandular hypertrophy, mucous cell metaplasia, and reduced numbers of zymogenic cells. In this study, we characterized gastric gland development in wild-type and Hip1r-deficient mice to define normal development, as well as the timing and sequence of the cellular transformation events in the mutant stomach. Postnatal (newborn to 8-wk-old) stomachs were examined by histological and gene expression analysis. At birth, gastric glands in wild-type and mutant mice were rudimentary and mature gastric epithelial cells were not apparent, although marker expression was detected for most cell lineages. Interestingly, newborns exhibited unusual cell types, including a novel surface cell filled with lipid and cells that coexpressed markers of mature mucous neck and zymogenic cells. Glandular morphogenesis proceeded rapidly in both genotypes, with gastric glands formed by weaning at 3 wk of age. In the Hip1r-deficient stomach, epithelial cell remodeling developed in a progressive manner. Initially, in the perinatal stomach, cellular changes were limited to parietal cell apoptosis. Other epithelial cell changes, including apoptotic loss of zymogenic cells and expansion of metaplastic mucous cells, emerged several weeks later when the glands were morphologically mature. Thus, parietal cell loss appeared to be the initiating event in Hip1r-deficient mice, with secondary remodeling of the other gastric epithelial cells.
Keeley
Theresa M
TM
Dept. of Molecular and Integrative Physiology, The Univ. of Michigan, Ann Arbor, 48109-2200, USA.
Samuelson
Linda C
LC
D048868:Adaptor Proteins, Signal Transducing; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004848:Epithelium / Q000254:growth & development / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006706:Homeostasis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins; D013047:Specific Pathogen-Free Organisms; D013270:Stomach / Q000166:cytology* / Q000254:growth & development*
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C489534:Hip1r protein, mouse; D008840:Microfilament Proteins
Am J Physiol. 1999 Oct;277(4):G773-84
10516143
Am J Physiol Gastrointest Liver Physiol. 2006 Nov;291(5):G762-5
17030897
Dig Dis Sci. 1996 Apr;41(4):773-84
8674399
Anat Rec. 1993 Jun;236(2):297-313
8338234
Am J Physiol Gastrointest Liver Physiol. 2008 May;294(5):G1105-8
18308861
Gastroenterology. 1970 Jul;59(1):22-35
5464013
Am J Physiol. 1981 Sep;241(3):G199-214
7025659
Gastroenterology. 2010 Feb;138(2):562-72, 572.e1-2
19883649
J Clin Invest. 1996 Oct 15;98(8):1918-29
8878444
Gastroenterology. 1992 Dec;103(6):1950-63
1451986
J Biol Chem. 1996 Feb 16;271(7):3671-6
8631979
Development. 2007 Jan;134(1):211-22
17164426
Development. 1995 Jan;121(1):149-61
7867496
Anat Rec. 1993 Jun;236(2):280-96
8338233
Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13687-92
11717430
Gastroenterology. 2007 May;132(5):1804-19
17484876
Lab Invest. 2005 May;85(5):702-15
15765119
Anat Rec. 1993 Jun;236(2):333-40
8338236
Anat Rec. 1993 Jun;236(2):259-79
8338232
Dev Biol. 2007 Mar 1;303(1):295-310
17196193
Am J Physiol Gastrointest Liver Physiol. 2005 Feb;288(2):G362-75
15647607
Am J Physiol Gastrointest Liver Physiol. 2006 Apr;290(4):G793-804
16306133
J Biol Chem. 2007 Nov 16;282(46):33265-33274
17872943
Anat Rec. 1993 Jun;236(2):314-32
8338235
Gastroenterology. 1998 Apr;114(4):675-89
9516388
Scand J Gastroenterol. 1971;6(4):329-33
5561179
J Biol Chem. 2000 Jul 14;275(28):21555-65
10764766
J Clin Invest. 2008 Jul;118(7):2459-70
18535670
Gastric Cancer. 2009;12(4):189-97
20047123
Am J Physiol. 1997 May;272(5 Pt 1):G1209-20
9176232
Biochem Soc Trans. 2010 Feb;38(Pt 1):187-91
20074057
Physiol Genomics. 2006 Jan 12;24(2):124-32
16278279
Gastroenterology. 2010 Feb;138(2):550-61, 561.e1-8
19909751
Annu Rev Physiol. 1985;47:199-215
3922287
Gastroenterology. 2006 Apr;130(4):1233-44
16618415
Arch Histol Jpn. 1984 Nov;47(5):459-74
6532366
Am J Physiol Gastrointest Liver Physiol. 2006 May;290(5):G970-9
16399875
Dev Biol. 2009 Jan 1;325(1):211-24
19013146