All Phenotypes Fam3d<em1Wko> MGI Mouse

homeostasis/metabolism phenotype ( J:304594 )

N	• mice show no obvious abnormalities in total cholesterol or triglyceride levels

abnormal cytokine level ( J:300819 )

• protein level of proinflammatory cytokines and chemokines, such as TNF-alpha and CCL2, are increased following DSS-induction of colitis

increased incidence of tumors by chemical induction ( J:300819 )

• in the chronic model of colitis with low doses of DSS, mice exhibit increased number of larger tumors in the colon, accompanied by the development of marked leukocyte infiltration, extensive hyperplastic and neoplastic foci especially near the mucosal surface in the colon

• in AOM/DSS-induced tumorigenesis, mice show more weight loss, shortened colon length, and increased number of larger tumors in the colon

• AOM/DSS-induced mice show more rapidly progressing colorectal cancer because of more numerous invasive glands in the distal colons that invade deeper into the mucosal wall

decreased susceptibility to injury ( J:304594 )

• mice show amelioration of elastase-induced abdominal aortic aneurysm development, showing no increase in the maximal diameters of infrarenal abdominal aortas after 14 days of elastase induction, attenuation of elastin degradation, inhibition of vascular smooth muscle cell apoptosis and maintain vascular smooth muscle cell content in the aortic wall, and attenuated ROS production

• mice exhibit attenuation of CaPO4-induced abdominal aortic aneurysm development, showing no CaPO4-induced infrarenal abdominal enlargement and elastin degradation

• the inhibition of neutrophil recruitment is seen at 3 days post elastase-induction which is earlier than the inhibition of Ly6C^high monocyte recruitment at 7 days and macrophage infiltration at 14 days

abnormal colon goblet cell morphology ( J:300819 )

• goblet cell hypotrophy and hypoplasia, with an increased number and size of goblet cells

abnormal intestinal goblet cell physiology ( J:300819 )

• goblet cell dysfunction occurs first as a shift from the production of acidic mucin toward neutral mucin in the colonic epithelium of newborns, followed by hyperplasia and a continuous mucin shift with aging (mucin retention over time)

enlarged spleen ( J:300819 )

• spleen is enlarged in 1-year-old mice

decreased neutrophil cell number ( J:304594 )

• the accumulation of neutrophils (CD45+CD11b+Ly6G+) in the infrarenal abdominal aortic wall at 3 and 7 days after elastase-induction is inhibited but the number of neutrophils in peripheral blood is increased

• however, no differences in the number of neutrophils in the bone marrow after elastase induction is seen compared to wild-type mice

decreased macrophage cell number ( J:304594 )

• a decrease in macrophage infiltration is seen after elastase induction

• however, no differences in inflammatory activation of macrophages are seen

decreased Ly6C high monocyte number ( J:304594 )

• a decrease in the degree of Ly6c^high monocyte recruitment is seen after elastase induction

• however, no differences in the numbers of monocytes in either peripheral blood or bone marrow are seen

increased leukocyte cell number ( J:300819 )

• 1-year-old mice show an increase in circulating inflammatory leukocytes

• colonic mucosa is infiltrated by a large number of leukocytes, including monocytes, macrophages, neutrophils, and T cells following DSS-induction of colitis

increased neutrophil cell number ( J:300819 , J:304594 )

	• 1-year old mice that develop spontaneous colitis show neutrophil infiltration into the colonic epithelium (J:300819)
	• number of neutrophils is elevated in the peripheral blood (J:304594) • the number of neutrophils in in peripheral blood is increased after elastase induction of abdominal aortic aneurysm (J:304594) • however the proportion of myeloid cells in bone marrow shows no differences (J:304594)

abnormal neutrophil physiology ( J:304594 )

• TNF-alpha-induced neutrophil adhesion, but not rolling, is inhibited

abnormal intestinal epithelium morphology ( J:300819 )

• proliferating cells show either a disorganized pattern, mainly in the middle and bottom of the crypts or have a diffuse distribution compared to wild-type mice which have abundant proliferating cells at the bottom of the colon crypts and reduced or absent in epithelial cells moving toward the top of the crypts

• however, there is no difference in the numbers of Lgr5+ epithelial stem cells in the colon

• 1-year old mice that develop spontaneous colitis show loss of differentiated epithelial cells

• DSS-treated mice show intestinal epithelial damage by day 5 with further deterioration by day 7

abnormal intestinal mucosa morphology ( J:300819 )

• mice exhibit defective mucosal integrity in colon, with thickness of the inner mucus layer significantly reduced

abnormal crypts of Lieberkuhn morphology ( J:300819 )

• colons exhibit crypt hyperplasia with elongated crypts; elongated crypts are not present at birth but appear progressively with age

• PAS+ goblet cells, normally found in the apical and central parts of the crypts, are present at the base of the crypts in the colon

• mice treated with antibiotics show elimination of the difference in colon crypt length

• mice show an increased ratio of sulfomucin to sialomucin in the crypts

abnormal colon goblet cell morphology ( J:300819 )

• goblet cell hypotrophy and hypoplasia, with an increased number and size of goblet cells

decreased intestinal mucosa thickness ( J:300819 )

• progressive reduction in the thickness of the mucus layer of distal colon, with a greater reduction in the inner mucus layer but without apparent bacterial invasion

abnormal colon morphology ( J:300819 )

• colon weight is increased in 1-year-old mice

decreased colon length ( J:300819 )

• DSS-treated mice show shortened colon length by day 5 with further deterioration by day 7

• mice treated with antibiotics show elimination of the difference in colon crypt length

abnormal gut flora balance ( J:300819 )

• mice show altered composition of microbiota in the colon; fecal microbiota contains an expanded abundance in Bacteroidetes, a higher abundance of Muribaculaceae and lower abundance of Ruminococcaceae and Deferribacteraceae

• colon shows an increased abundance in Lactobacillus/Lactococcus and Peptostreptococcus in Firmicutes, but decreased Segmented filamentous bacteria, Eubacterium rectale, Enterococcus faecalis in Firmicutes, and Enterobacteria in Proteobacteria

abnormal intestinal epithelium physiology ( J:300819 )

• mice show an increase in proliferating epithelial cells in the colonic mucosa

• colon shows reduced epithelial cell proliferation with increased apoptosis after 7-day DSS intake

abnormal intestinal goblet cell physiology ( J:300819 )

• goblet cell dysfunction occurs first as a shift from the production of acidic mucin toward neutral mucin in the colonic epithelium of newborns, followed by hyperplasia and a continuous mucin shift with aging (mucin retention over time)

colitis ( J:300819 )

• mice develop spontaneous colitis by 1 year of age

• mice exhibit infiltration of CD3+ T and B220+ B cells in the colonic epithelium, indicating the presence of low-level lymphocytic inflammation

• increase in CD11b+ myeloid and CD3+ T cells in the colon of 1-year-old mice

• however, the number of F4/80+ macrophages in the colon is normal and no acute inflammation with neutrophil infiltration is seen

increased susceptibility to induced colitis ( J:300819 )

• mice exhibit increased severity of DSS-induced acute colitis, showing increased inflammation, more rapid body weight loss, increased rectal bleeding, and diarrhea

• in a chronic model of colitis induced by lower doses of DSS, mice show increased severity of chronic colitis, with reduced colon length, body weight and survival

• rectal infusion with an adenovirus expressing FAM3D ameliorates established colitis

• mice treated with antibiotics show reduction in the severity of colitis, however they still show a persistent mild degree of colitis with mucosal damage and lower leukocyte infiltration on day 5 after DSS treatment

increased susceptibility to colitis induced morbidity/mortality ( J:300819 )

• all DSS-induced mice die by day 9 of induction compared to day 12 in wild-type mice

• mice treated with a lower level of DSS (2.5%) still fail to recover and die by day 9

• in a chronic model of colitis induced by lower doses of DSS, mice show reduced survival compared to wild-type mice

abnormal crypts of Lieberkuhn morphology ( J:300819 )

• colons exhibit crypt hyperplasia with elongated crypts; elongated crypts are not present at birth but appear progressively with age

• PAS+ goblet cells, normally found in the apical and central parts of the crypts, are present at the base of the crypts in the colon

• mice treated with antibiotics show elimination of the difference in colon crypt length

• mice show an increased ratio of sulfomucin to sialomucin in the crypts

abnormal colon goblet cell morphology ( J:300819 )

• goblet cell hypotrophy and hypoplasia, with an increased number and size of goblet cells

colitis ( J:300819 )

• mice develop spontaneous colitis by 1 year of age

• mice exhibit infiltration of CD3+ T and B220+ B cells in the colonic epithelium, indicating the presence of low-level lymphocytic inflammation

• increase in CD11b+ myeloid and CD3+ T cells in the colon of 1-year-old mice

• however, the number of F4/80+ macrophages in the colon is normal and no acute inflammation with neutrophil infiltration is seen

increased susceptibility to induced colitis ( J:300819 )

• mice exhibit increased severity of DSS-induced acute colitis, showing increased inflammation, more rapid body weight loss, increased rectal bleeding, and diarrhea

• in a chronic model of colitis induced by lower doses of DSS, mice show increased severity of chronic colitis, with reduced colon length, body weight and survival

• rectal infusion with an adenovirus expressing FAM3D ameliorates established colitis

• mice treated with antibiotics show reduction in the severity of colitis, however they still show a persistent mild degree of colitis with mucosal damage and lower leukocyte infiltration on day 5 after DSS treatment

increased susceptibility to colitis induced morbidity/mortality ( J:300819 )

• all DSS-induced mice die by day 9 of induction compared to day 12 in wild-type mice

• mice treated with a lower level of DSS (2.5%) still fail to recover and die by day 9

• in a chronic model of colitis induced by lower doses of DSS, mice show reduced survival compared to wild-type mice

enlarged spleen ( J:300819 )

• spleen is enlarged in 1-year-old mice

decreased neutrophil cell number ( J:304594 )

• the accumulation of neutrophils (CD45+CD11b+Ly6G+) in the infrarenal abdominal aortic wall at 3 and 7 days after elastase-induction is inhibited but the number of neutrophils in peripheral blood is increased

• however, no differences in the number of neutrophils in the bone marrow after elastase induction is seen compared to wild-type mice

decreased macrophage cell number ( J:304594 )

• a decrease in macrophage infiltration is seen after elastase induction

• however, no differences in inflammatory activation of macrophages are seen

decreased Ly6C high monocyte number ( J:304594 )

• a decrease in the degree of Ly6c^high monocyte recruitment is seen after elastase induction

• however, no differences in the numbers of monocytes in either peripheral blood or bone marrow are seen

increased leukocyte cell number ( J:300819 )

• 1-year-old mice show an increase in circulating inflammatory leukocytes

• colonic mucosa is infiltrated by a large number of leukocytes, including monocytes, macrophages, neutrophils, and T cells following DSS-induction of colitis

increased neutrophil cell number ( J:300819 , J:304594 )

	• 1-year old mice that develop spontaneous colitis show neutrophil infiltration into the colonic epithelium (J:300819)
	• number of neutrophils is elevated in the peripheral blood (J:304594) • the number of neutrophils in in peripheral blood is increased after elastase induction of abdominal aortic aneurysm (J:304594) • however the proportion of myeloid cells in bone marrow shows no differences (J:304594)

abnormal neutrophil physiology ( J:304594 )

• TNF-alpha-induced neutrophil adhesion, but not rolling, is inhibited

abnormal cytokine level ( J:300819 )

• protein level of proinflammatory cytokines and chemokines, such as TNF-alpha and CCL2, are increased following DSS-induction of colitis

enlarged spleen ( J:300819 )

• spleen is enlarged in 1-year-old mice

cardiovascular system phenotype ( J:304594 )

N	• mice show no obvious abnormalities in blood pressure

increased susceptibility to colitis induced morbidity/mortality ( J:300819 )

• all DSS-induced mice die by day 9 of induction compared to day 12 in wild-type mice

• mice treated with a lower level of DSS (2.5%) still fail to recover and die by day 9

• in a chronic model of colitis induced by lower doses of DSS, mice show reduced survival compared to wild-type mice

increased incidence of tumors by chemical induction ( J:300819 )

• in the chronic model of colitis with low doses of DSS, mice exhibit increased number of larger tumors in the colon, accompanied by the development of marked leukocyte infiltration, extensive hyperplastic and neoplastic foci especially near the mucosal surface in the colon

• in AOM/DSS-induced tumorigenesis, mice show more weight loss, shortened colon length, and increased number of larger tumors in the colon

• AOM/DSS-induced mice show more rapidly progressing colorectal cancer because of more numerous invasive glands in the distal colons that invade deeper into the mucosal wall

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

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