Phenotypes associated with this allele

• Allele Symbol: Hoxa11os^em1Kaf
• Allele Name: endonuclease-mediated mutation 1, Katherine A Fitzgerald
• Allele ID: MGI:7738733
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hoxa11os^em1Kaf/Hoxa11os^em1Kaf	C57BL/6-Hoxa11os^em1Kaf	MGI:7783619

Genotype
MGI:7783619

hm1

• Allelic Composition: Hoxa11os^em1Kaf/Hoxa11os^em1Kaf
• Genetic Background: C57BL/6-Hoxa11os^em1Kaf

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

digestive/alimentary system

digestive/alimentary phenotype ( J:344661 )

N • mice show no differences in family-level relative abundance of fecal microbiota flora relative to wild-type controls, indicating normal colonization of microbiota in the intestine under homeostatic conditions

diarrhea ( J:344661 )

• at 4 months of age, mice exhibit diarrhea

melena ( J:344661 )

• at 4 months of age, mice exhibit blood in their feces

intestinal inflammation ( J:344661 )

• mice develop mild signs of spontaneous intestinal inflammation as they age, with significantly higher expression levels of pro-inflammatory cytokines (Il6, Il1b, and Ccl5) in the colon at 4 months of age

• however, body weight, colon length, colon histology, immune cell composition, and intestinal epithelial cell (IEC) composition are similar to those in wild-type controls

increased susceptibility to induced colitis ( J:344661 )

• following acute dextran sodium sulfate (DSS)-induced colitis (2% DSS for 7 days), both sexes show significantly shorter colon length, greater weight loss, higher scores for stool appearance, higher pathological scores, higher expression levels of pro-inflammatory cytokines (Il6, Il1b, and Cxcl10) and interferon-stimulated genes (Cxcl1, Ccl5 and Mx1), and a lower number of Ki67+ cells in the distal colon than DSS-treated wild-type controls

• in a recovery model of DSS-induced colitis (1.5% DSS for 5 days, followed by regular water for 7 days), mice still exhibit severe colitis, with shorter colon lengths, diarrhea and traces of blood in the feces, greater weight loss, and higher pathological scores than similarly treated wild-type controls

• following Salmonella typhimurium-induced colitis, mice exhibit shorter colon lengths, greater weight loss, higher stool appearance and pathological scores, and increased expression levels of Il6, Il1b, and Cxcl10 in the colon than similarly infected wild-type controls

• treatment with the mtROS scavenger MitoQ ameliorates DSS-induced colitis and restores colon length, weight loss, blood and diarrhea, pathological scores, and proinflammatory cytokines to wild-type control levels

• treatment with the complex I inhibitor rotenone has no further impact on DSS-treated mice

cellular

abnormal mitochondrial morphology ( J:344661 )

• mitochondria from colonic LP myeloid cells are swollen and show disrupted cristae and loss of matrix density relative to wild-type cells

• in contrast, colonic IECs mitochondria appear intact

decreased mitochondrial DNA content ( J:344661 )

• colonic CD45+ lamina propria (LP) immune cells isolated from 4.5-mo-old mice show reduced levels of mitochondrial DNA (mtDNA)

• however, no changes in mtDNA levels are found in CD45- intestinal epithelial cells (IECs)

abnormal mitochondrial crista morphology ( J:344661 )

• mitochondria from colonic LP myeloid cells show disrupted cristae

abnormal mitochondrial matrix morphology ( J:344661 )

• mitochondria from colonic LP myeloid cells show loss of matrix density

decreased mitochondrial size ( J:344661 )

• isolated colonic CD45+ CD11b+ myeloid cells show a significant decrease in mitochondrial mass relative to wild-type myeloid cells

• however, no further reduction of mitochondrial mass is seen in myeloid cells treated with rotenone (a complex I inhibitor), indicating that complex I activity is already impaired

• CD45+ CD11b- lymphocytes, and CD45- EPCM+ IECs show normal mitochondrial mass relative to wild-type cells

dilated mitochondrion ( J:344661 )

• mitochondria from colonic LP myeloid cells appear swollen

abnormal mitochondrial physiology ( J:344661 )

• isolated colonic CD45+ CD11b+ myeloid cells show a significant decrease in mitochondrial membrane potential relative to wild-type myeloid cells

• however, no further reduction of mitochondrial mass is seen in rotenone-treated myeloid cells

• CD45+ CD11b- lymphocytes, and CD45- EPCM+ IECs show normal mitochondrial membrane potentials relative to wild-type cells

abnormal oxidative phosphorylation ( J:344661 )

• mice show impaired oxidative phosphorylation (OXPHOS) in the colon

abnormal mitochondrial ATP synthesis coupled electron transport ( J:344661 )

• CD45+ lamina propria (LP) immune cells and CD45- intestinal epithelial cells (IECs) isolated from the distal colon of 4.5-mo-old mice show a reduced NAD+/NADH ratio, suggesting impaired ETC complex I activity; impaired conversion of NADH to NAD is coupled with a reduction in ATP production

oxidative stress ( J:344661 )

• colonic CD45+ lamina propria (LP) immune cells and CD45- intestinal epithelial cells (IECs) isolated from 4.5-mo-old mice show increased levels of mitochondrial reactive oxygen species

immune system

intestinal inflammation ( J:344661 )

• mice develop mild signs of spontaneous intestinal inflammation as they age, with significantly higher expression levels of pro-inflammatory cytokines (Il6, Il1b, and Ccl5) in the colon at 4 months of age

• however, body weight, colon length, colon histology, immune cell composition, and intestinal epithelial cell (IEC) composition are similar to those in wild-type controls

increased susceptibility to induced colitis ( J:344661 )

• following acute dextran sodium sulfate (DSS)-induced colitis (2% DSS for 7 days), both sexes show significantly shorter colon length, greater weight loss, higher scores for stool appearance, higher pathological scores, higher expression levels of pro-inflammatory cytokines (Il6, Il1b, and Cxcl10) and interferon-stimulated genes (Cxcl1, Ccl5 and Mx1), and a lower number of Ki67+ cells in the distal colon than DSS-treated wild-type controls

• in a recovery model of DSS-induced colitis (1.5% DSS for 5 days, followed by regular water for 7 days), mice still exhibit severe colitis, with shorter colon lengths, diarrhea and traces of blood in the feces, greater weight loss, and higher pathological scores than similarly treated wild-type controls

• following Salmonella typhimurium-induced colitis, mice exhibit shorter colon lengths, greater weight loss, higher stool appearance and pathological scores, and increased expression levels of Il6, Il1b, and Cxcl10 in the colon than similarly infected wild-type controls

• treatment with the mtROS scavenger MitoQ ameliorates DSS-induced colitis and restores colon length, weight loss, blood and diarrhea, pathological scores, and proinflammatory cytokines to wild-type control levels

• treatment with the complex I inhibitor rotenone has no further impact on DSS-treated mice

abnormal cytokine secretion ( J:344661 )

• at 4 months of age, mice show significantly higher expression levels of pro-inflammatory cytokines (Il6, Il1b, and Ccl5) than wild-type controls

• after treatment with 2% DSS for 7 days, mice show significantly higher expression levels of pro-inflammatory cytokines (Il6, Il1b, and Cxcl10) and interferon-stimulated genes (Cxcl1, Ccl5 and Mx1) in the colon than DSS-treated wild-type controls

• colonic CD11b+ myeloid cells isolated from older mice show significantly higher expression levels of Il6, Il1b, and Cxcl10 than myeloid cells from wild-type controls

homeostasis/metabolism

decreased oxygen consumption ( J:344661 )

• under basal conditions, colonic cells isolated from the distal colon of 4-mo-old mice show a significantly lower oxygen consumption rate (OCR) than wild-type cells