Phenotypes associated with this allele

• Allele Symbol: Jak1^M1Mhda
• Allele Name: mutation 1, Martin Hrabe de Angelis
• Allele ID: MGI:5526094
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Jak1^M1Mhda/Jak1^M1Mhda	C3HeB/FeJ-Jak1^M1Mhda/Ieg	MGI:5425538
ht2	Jak1^M1Mhda/Jak1^+	C3HeB/FeJ-Jak1^M1Mhda	MGI:5526095

Genotype
MGI:5425538

hm1

• Allelic Composition: Jak1^M1Mhda/Jak1^M1Mhda
• Genetic Background: C3HeB/FeJ-Jak1^M1Mhda/Ieg

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

craniofacial

abnormal outer ear morphology ( J:183993 )

• auricle degeneration when >4 months old

growth/size/body

abnormal outer ear morphology ( J:183993 )

• auricle degeneration when >4 months old

decreased body size ( J:183993 )

hearing/vestibular/ear

abnormal outer ear morphology ( J:183993 )

• auricle degeneration when >4 months old

homeostasis/metabolism

increased circulating calcium level ( J:183993 )

decreased circulating phosphate level ( J:183993 )

increased circulating alkaline phosphatase level ( J:183993 )

Genotype
MGI:5526095

ht2

• Allelic Composition: Jak1^M1Mhda/Jak1⁺
• Genetic Background: C3HeB/FeJ-Jak1^M1Mhda

growth/size/body

abnormal outer ear morphology ( J:199153 )

• starting at 4 months of age, pinnae shrink with slow progression

• with age, the ear margins show redness and thickening

decreased birth body size ( J:199153 )

decreased body weight ( J:199153 )

• at 10 and 15 weeks of age

liver hyperplasia ( J:199153 )

• nodular regenerative hyperplasia of the liver

enlarged spleen ( J:199153 )

♀ • females exhibit splenomegaly

♀ • however, architecture of the white pulp and cell composition appear normal and show normal T cell, B cell and macrophage frequencies

cardiovascular system

abnormal liver vasculature morphology ( J:199153 )

• livers show prominent vessels and increased vascularization at 4-12 months of age

dilated liver sinusoidal space ( J:199153 )

• sinusoidal dilatation

craniofacial

abnormal outer ear morphology ( J:199153 )

• starting at 4 months of age, pinnae shrink with slow progression

• with age, the ear margins show redness and thickening

hearing/vestibular/ear

abnormal outer ear morphology ( J:199153 )

• starting at 4 months of age, pinnae shrink with slow progression

• with age, the ear margins show redness and thickening

ear inflammation ( J:199153 )

• ear cartilage is destroyed by inflammatory cells in advanced lesions

hematopoietic system

enlarged spleen ( J:199153 )

♀ • females exhibit splenomegaly

♀ • however, architecture of the white pulp and cell composition appear normal and show normal T cell, B cell and macrophage frequencies

microcytic anemia ( J:199153 )

• microcytic, erythropenic anemia with increased anisocytosis and reticulocyte proportion

decreased megakaryocyte cell number ( J:199153 )

• 50% and 75% loss of megakaryoctyes in the spleen red pulp of females and males, respectively

increased erythrocyte cell number ( J:199153 )

• increase in red blood cell counts at 4.5 and 6 months of age

decreased cellular hemoglobin content ( J:199153 )

decreased mean corpuscular volume ( J:199153 )

anisocytosis ( J:199153 )

• anisocytosis is seen at 4.5 and 6 months of age

thrombocytopenia ( J:199153 )

• older mutants exhibit thrombocytopenia which is associated with increased platelet distribution width

decreased mean platelet volume ( J:199153 )

abnormal plasma cell morphology ( J:199153 )

♀ • increase in the number of Russell bodies (large cytoplasmic eosiniophilic globules containing immunoglobulin inclusions) in females

increased plasma cell number ( J:199153 )

• slight increase in the number of plasma cells

increased immunoglobulin level ( J:199153 )

• females show significant elevations in IgA, IgG1, IgG2a, and IgM and a tendency towards increased IgG3 and IgE levels

• males show significant elevations in IgG1, IgG2a, and IgM and a tendency towards increased levels of IgA, IgG3, and IgE

increased IgA level ( J:199153 )

• significant elevation in females and a tendency towards increased levels in males

increased IgG1 level ( J:199153 )

• significant elevations in both males and females

increased IgG2a level ( J:199153 )

• significant elevations in both males and females

increased IgM level ( J:199153 )

• significant elevations in both males and females

immune system

enlarged spleen ( J:199153 )

♀ • females exhibit splenomegaly

♀ • however, architecture of the white pulp and cell composition appear normal and show normal T cell, B cell and macrophage frequencies

ear inflammation ( J:199153 )

• ear cartilage is destroyed by inflammatory cells in advanced lesions

abnormal plasma cell morphology ( J:199153 )

♀ • increase in the number of Russell bodies (large cytoplasmic eosiniophilic globules containing immunoglobulin inclusions) in females

increased plasma cell number ( J:199153 )

• slight increase in the number of plasma cells

increased immunoglobulin level ( J:199153 )

• females show significant elevations in IgA, IgG1, IgG2a, and IgM and a tendency towards increased IgG3 and IgE levels

• males show significant elevations in IgG1, IgG2a, and IgM and a tendency towards increased levels of IgA, IgG3, and IgE

increased IgA level ( J:199153 )

• significant elevation in females and a tendency towards increased levels in males

increased IgG1 level ( J:199153 )

• significant elevations in both males and females

increased IgG2a level ( J:199153 )

• significant elevations in both males and females

increased IgM level ( J:199153 )

• significant elevations in both males and females

increased anti-nuclear antigen antibody level ( J:199153 )

• presence of anti-DNA autoantibodies

skin inflammation ( J:199153 )

• 60% of mutants at 8 months of age show mononuclear cell infiltration in the dermis

integument

skin inflammation ( J:199153 )

• 60% of mutants at 8 months of age show mononuclear cell infiltration in the dermis

alopecia ( J:199153 )

♀ • females, but not males, develop alopecia on the neck and head, with external signs of inflammation in some mutants

abnormal dermal layer morphology ( J:199153 )

• dermis shows thickening of connective tissue, increase in granulation tissue, and mononuclear cell infiltration

skin lesions ( J:199153 )

• skin lesions of the upper dorsal region and of the ears show inflammatory infiltrate (predominately neutrophils) in the epidermis with hyperkeratosis and acantosis

limbs/digits/tail

abnormal tail morphology ( J:199153 )

• redness and thickening of tails is seen after 8 months of age in some mutants

liver/biliary system

abnormal liver morphology ( J:199153 )

• livers of 74% of mutants show irregular margins, prominent vessels and increased vascularization at 4 months of age and by 12 months, 90% of mutants show these changes

abnormal liver vasculature morphology ( J:199153 )

• livers show prominent vessels and increased vascularization at 4-12 months of age

dilated liver sinusoidal space ( J:199153 )

• sinusoidal dilatation

liver hyperplasia ( J:199153 )

• nodular regenerative hyperplasia of the liver

abnormal hepatocyte morphology ( J:199153 )

• hyperplastic hepatocytes surrounded by atrophic hepatocytes in the adjacent parenchyma

enhanced liver regeneration ( J:199153 )

• lesions resemble nodular regenerative hyperplasia

homeostasis/metabolism

abnormal circulating creatinine level ( J:199153 )

• plasma creatinine is increased in males at 12 weeks of age, but decreased in females at 36 weeks of age, and decreased in both males and females at 52 weeks of age

increased blood uric acid level ( J:199153 )

• plasma uric acid is elevated at 3 months of age in both males and females but only in females at 6 months of age

hypoglycemia ( J:199153 )

• from 6 months of age on

decreased circulating parathyroid hormone level ( J:199153 )

• parathyroid hormone plasma concentrations are lower in 12 week old mice

decreased circulating cholesterol level ( J:199153 )

increased circulating calcium level ( J:199153 )

♂ • only males exhibit hypercalcemia at 12 and 24 weeks of age

decreased circulating phosphate level ( J:199153 )

• hypophosphatemia is seen at 12, 24, 36, and 52 weeks of age

• however mutants exhibit normal phosphate, calcium and creatinine urine excretion

decreased circulating serum albumin level ( J:199153 )

♀ • plasma albumin levels are decreased in females at 52 weeks of age

decreased circulating total protein level ( J:199153 )

• females show a decreases in total protein in plasma at 12 weeks of age and males at 24 weeks of age

decreased triglyceride level ( J:199153 )

decreased urine urea nitrogen level ( J:199153 )

• decrease in urea at 3 months of age, although this improves with age

increased alkaline phosphatase activity ( J:199153 )

renal/urinary system

decreased urine urea nitrogen level ( J:199153 )

• decrease in urea at 3 months of age, although this improves with age

abnormal glomerular mesangium morphology ( J:199153 )

• thickening of mesangium in some glomeruli

skeleton

decreased bone mineral density ( J:199153 )

• osteopenic bones

abnormal compact bone morphology ( J:199153 )

• in cortical bone, periosteal volume, cortical bone volume, and cross-sectional thickness are decreased and endosteal volume is increased

decreased compact bone volume ( J:199153 )

abnormal bone trabecula morphology ( J:199153 )

• decrease in trabecular density, trabecular content, bone volume:tissue ratio, trabecular bone surface, and trabecular number for trabecular bone

decreased bone trabecula number ( J:199153 )

• mutants at 12 months of age show loss of almost all metaphyseal and diaphyseal trabeculae

abnormal bone resorption ( J:199153 )

• mutants show increased values of collagen type I fragments generated during osteoclastic bone resorption

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
systemic lupus erythematosus		DOID:9074	OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420	J:199153