|
Allele Symbol Allele Name Allele ID |
Adam17tm1.2Bbl targeted mutation 1.2, Carl P Blobel MGI:4354847 |
||||||||||||||||||||||||
| Summary |
5 genotypes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increase in transepidermal water loss indicating barrier dysfunction
|
|
• dry skin progresses to eczematous lesion (eczematous dermatitis)
• skin lesions show mononuclear cell infiltrates including lymphocytes and mast cells
• epidermal T cell composition is altered, with dendritic epidermal T cells, a resident Vgamma5+ gammadelta T cell subset in epidermis, replaced by massive infiltration of Vgamma5neg gammadelta TCRmid T cells and CD4+ T cells
• about 20% of Vgamma5neg gammadelta TCRmid T cells express Vgamma4, but the majority do not
• analysis of infiltrating T cells shows that epidermal CD4 T cells consist of Th17 and Th22 cells, and the majority of Vgamma5neg gammadelta TCRmid T cells produce interleukin-17 (gammadeltaT17) and a fraction of which also produce interleukin-22
• mice treated with the antibiotics cefazolin and enrofloxacin after weaning are almost completely protected from developing eczematous lesions, however skin inflammation develops upon antibiotic withdrawal
• mice treated with antibiotics at 10 weeks after birth show improvement in eczematous dermatitis and inflammation
|
|
• mice exhibit altered skin microbiota, with a striking overgrowth of S. aureus which is seen within stratum corneum and follicular openings
• skin microbiota undergoes a sequential change where dysbiosis starts with the emergence of Corynebacterium mastitidis and then S. aureus and Corynebacterium bovis predominating later
• antibiotic-treated mice exhibit a higher bacterial diversity, with a reduction in S. aureus and C. bovis, however, withdrawal of antibiotics leads to skin microbiome dysbiosis
• mice treated with antibiotics at 10 weeks after birth show reversal of skin microbiome dysbiosis
|
|
• epidermal T cell composition is altered, with dendritic epidermal T cells, a resident Vgamma5+ gammadelta T cell subset in epidermis, replaced by massive infiltration of Vgamma5neg gammadelta TCRmid T cells and CD4+ T cells
• antibiotic treatment normalizes epidermal gammadelta T cell constituents
• antibiotic treatment does not affect CD4+ T cell numbers in the epidermis and they remain high, however these T cells produce less IL-4 and do not produce IL-17A or IL-22
|
|
• mice develop intense pruritus
|
|
• cytokine expression analysis in skin draining lymph nodes indicates an increase in numbers of Th1 cells
|
|
• cytokine expression analysis in skin draining lymph nodes indicates a prominent increase in Th17 cells
• antibiotic treated mice show a reduction in the numbers of Th17 cells in skin draining lymph nodes
|
|
• cytokine expression analysis in skin draining lymph nodes indicates an increase in numbers of Th2 cells
• antibiotic treated mice show a reduction in the numbers of Th2 cells in skin draining lymph nodes
|
|
• serum IgE levels are elevated
• mice treated with the antibiotics cefazolin and enrofloxacin after weaning have lower serum IgE concentrations
|
|
• CCL17, a T helper 2 cell chemokine, levels are elevated
|
|
• dry skin progresses to eczematous lesion (eczematous dermatitis)
• skin lesions show mononuclear cell infiltrates including lymphocytes and mast cells
• epidermal T cell composition is altered, with dendritic epidermal T cells, a resident Vgamma5+ gammadelta T cell subset in epidermis, replaced by massive infiltration of Vgamma5neg gammadelta TCRmid T cells and CD4+ T cells
• about 20% of Vgamma5neg gammadelta TCRmid T cells express Vgamma4, but the majority do not
• analysis of infiltrating T cells shows that epidermal CD4 T cells consist of Th17 and Th22 cells, and the majority of Vgamma5neg gammadelta TCRmid T cells produce interleukin-17 (gammadeltaT17) and a fraction of which also produce interleukin-22
• mice treated with the antibiotics cefazolin and enrofloxacin after weaning are almost completely protected from developing eczematous lesions, however skin inflammation develops upon antibiotic withdrawal
• mice treated with antibiotics at 10 weeks after birth show improvement in eczematous dermatitis and inflammation
|
|
• cytokine expression analysis in skin draining lymph nodes indicates an increase in numbers of Th1 cells
|
|
• cytokine expression analysis in skin draining lymph nodes indicates a prominent increase in Th17 cells
• antibiotic treated mice show a reduction in the numbers of Th17 cells in skin draining lymph nodes
|
|
• cytokine expression analysis in skin draining lymph nodes indicates an increase in numbers of Th2 cells
• antibiotic treated mice show a reduction in the numbers of Th2 cells in skin draining lymph nodes
|
|
• serum IgE levels are elevated
• mice treated with the antibiotics cefazolin and enrofloxacin after weaning have lower serum IgE concentrations
|
|
• CCL17, a T helper 2 cell chemokine, levels are elevated
|
|
• increase in transepidermal water loss indicating barrier dysfunction
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| atopic dermatitis | DOID:3310 |
OMIM:603165 OMIM:PS603165 |
J:229771 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• some animals die by 5 months of age, but the majority survive past 5 months
|
|
• after 12 weeks of age, body weight of animals is decreased compared to controls
|
|
• mice show retarded growth
|
|
• spleen is proportionately larger by 8 weeks
|
|
• hematopoiesis occurs in spleen (resulting is splenomegaly) and liver (which becomes more prominent with age)
|
|
• marrow is hypercellular
|
|
• at 8 weeks
|
|
• at 8 weeks
|
|
• at 8 weeks
|
|
• white blood cell number is decreased compared to controls at 8 weeks
|
|
• relative decrease compared to controls is observed at 8 weeks
|
|
• relative decrease compared to controls is observed at 8 weeks
|
|
• at 8 weeks
|
|
• increased compared to controls
|
|
• increased compared to controls
|
|
• lymphoid follicle development is retarded in 3 week-old mice; at 8 weeks, lymphoid follicles have developed to comparable extent as controls
|
|
• spleen is proportionately larger by 8 weeks
|
|
• by 8 weeks, expansion of spleen red pulp amount leads to splenomegaly
|
|
• white blood cell number is decreased compared to controls at 8 weeks
|
|
• relative decrease compared to controls is observed at 8 weeks
|
|
• relative decrease compared to controls is observed at 8 weeks
|
|
• at 8 weeks
|
|
• increased compared to controls
|
|
• increased compared to controls
|
|
• lymphoid follicle development is retarded in 3 week-old mice; at 8 weeks, lymphoid follicles have developed to comparable extent as controls
|
|
• spleen is proportionately larger by 8 weeks
|
|
• by 8 weeks, expansion of spleen red pulp amount leads to splenomegaly
|
|
• serum Il17 is significantly elevated
|
|
• levels of Il17 are highly elevated compared to controls due to increase in Il17 producing cells
|
|
• serum Il17 is significantly elevated
|
 |
• females are sterile
|
 |
• male fertility is severely impaired
|
|
• femur length is 10-15% shorter than controls
|
|
• zone is shorter than in controls
|
|
• zone is elongated; elongation is prominent at 2-3 weeks of age, and is less evident in older animals
|
|
• bones are shorter than in controls
|
|
• femur length is 10-15% shorter than controls
|
|
• metatarsi remained filled with bone marrow cells at least up to 4 months postnatal, whereas bone marrow in control bones is replaced by adipose tissue beginning around 3 weeks of age, and is completely filled with fat cells by 8 weeks after birth
|
|
• beginning at 8 weeks, animals have less cortical bone
|
|
• beginning at 8 weeks, animals have less trabecular bone
|
|
• bone mass of femur is decreased compared to controls
|
|
• animals show high-turnover type osteoporosis (characterized by increased osteoclast and osteoblast activities by about 8 weeks of age)
|
|
• osteoclast-related (eroded surfaces, osteoclast numbers, and osteoclast surfaces) and osteoblast-related (osteoid volume, osteoid surfaces, and osteoblast surfaces) parameters are increased compared to controls
|
|
• mice are born with their eyes open
|
|
• mice have hair defects
|
|
• mice show skin defects
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop eczematous dermatitis
|
|
• mice develop eczematous dermatitis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop eczematous dermatitis
|
|
• mice develop eczematous dermatitis
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
||
|
Citing These Resources Funding Information Warranty Disclaimer, Privacy Notice, Licensing, & Copyright Send questions and comments to User Support. |
last database update 04/23/2024 MGI 6.23 |
|
|
|
||
Analysis Tools