Phenotypes associated with this allele

• Allele Symbol: Chuk^tm2Mka
• Allele Name: targeted mutation 2, Michael Karin
• Allele ID: MGI:3045616
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Chuk^tm2Mka/Chuk^tm2Mka	B6.Cg-Chuk^tm2Mka	MGI:3841113
hm2	Chuk^tm2Mka/Chuk^tm2Mka	Not Specified	MGI:3045813
cx3	Chuk^tm2Mka/Chuk^tm2Mka Tg(Tnfsf13b)1Fma/?	B6.Cg-Chuk^tm2Mka Tg(Tnfsf13b)1Fma	MGI:3841107
cx4	Chuk^tm2Mka/Chuk^tm2Mka Tg(MMTV-CCND1)1Esmp/?	Not Specified	MGI:3847938

Genotype
MGI:3841113

hm1

• Allelic Composition: Chuk^tm2Mka/Chuk^tm2Mka
• Genetic Background: B6.Cg-Chuk^tm2Mka

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

immune system

abnormal B cell physiology ( J:113556 )

• there is about a 25% reduction in the number of B cells that survive 36 hours of in vitro culturing compared to controls

• addition of Tnfsf13b (BAFF) to the culture slightly elevates survival but not to the same extent as with wild-type B cells

hematopoietic system

abnormal B cell physiology ( J:113556 )

• there is about a 25% reduction in the number of B cells that survive 36 hours of in vitro culturing compared to controls

• addition of Tnfsf13b (BAFF) to the culture slightly elevates survival but not to the same extent as with wild-type B cells

Genotype
MGI:3045813

hm2

• Allelic Composition: Chuk^tm2Mka/Chuk^tm2Mka
• Genetic Background: Not Specified

endocrine/exocrine glands

abnormal mammary gland growth during pregnancy ( J:90978 )

♀ • virgin females complete normal ductal development, however, on day 1 after delivery, the lobuloalveolar network in mammary gland is severely underdeveloped, with minimal side branching and alveoli sprouting of ducts

abnormal mammary gland epithelium morphology ( J:90978 )

♀ • epithelial cell proliferation is impaired, with the proliferation rate in the mammary epithelium about half of the wild-type rate at P10 and decreased even further on day 1 after delivery

♀ • most of the proliferation rate decrease is due to reduced proliferation of lobuloalveolar cells

abnormal mammary gland alveolus morphology ( J:90978 )

♀ • number of secretory alveoli is reduced and the alveoli are small with small or closed lumina in females on day 1 after delivery

abnormal lactation ( J:90978 )

♀ • all pups born to mutant mothers die within 1-2 days, and despite normal nursing pups do not contain milk in stomachs, indicating a lactation defect

reproductive system

abnormal mammary gland growth during pregnancy ( J:90978 )

♀ • virgin females complete normal ductal development, however, on day 1 after delivery, the lobuloalveolar network in mammary gland is severely underdeveloped, with minimal side branching and alveoli sprouting of ducts

integument

abnormal mammary gland growth during pregnancy ( J:90978 )

♀ • virgin females complete normal ductal development, however, on day 1 after delivery, the lobuloalveolar network in mammary gland is severely underdeveloped, with minimal side branching and alveoli sprouting of ducts

abnormal mammary gland epithelium morphology ( J:90978 )

♀ • epithelial cell proliferation is impaired, with the proliferation rate in the mammary epithelium about half of the wild-type rate at P10 and decreased even further on day 1 after delivery

♀ • most of the proliferation rate decrease is due to reduced proliferation of lobuloalveolar cells

abnormal mammary gland alveolus morphology ( J:90978 )

♀ • number of secretory alveoli is reduced and the alveoli are small with small or closed lumina in females on day 1 after delivery

abnormal lactation ( J:90978 )

♀ • all pups born to mutant mothers die within 1-2 days, and despite normal nursing pups do not contain milk in stomachs, indicating a lactation defect

Genotype
MGI:3841107

cx3

• Allelic Composition: Chuk^tm2Mka/Chuk^tm2Mka; Tg(Tnfsf13b)1Fma/?
• Genetic Background: B6.Cg-Chuk^tm2Mka Tg(Tnfsf13b)1Fma

immune system

increased transitional stage B cell number ( J:113556 )

• numbers of T2 B cells are slightly enlarged in the spleen

decreased marginal zone B cell number ( J:113556 )

• marginal zone B cell numbers are reduced compared to controls

absent spleen marginal zone ( J:113556 )

• marginal zones could not be localized in these mice

abnormal B cell activation ( J:113556 )

• B cells have a strong response to T cell independent antigens producing higher levels of antigen-specific IgM, IgG2a, IgG2b class antibodies than wild-type controls

• however, there is no significant elevation of antigen-specific IgG1, IgG3, and IgA antibodies as is observed in transgenic mice on a wild-type background

• levels of antibodies produced are also lower than those in transgenic mice on a wild-type background

increased anti-double stranded DNA antibody level ( J:113556 )

• anti-dsDNA antibodies of the IgM class are found in circulation

• titers of these auto-antibodies increase slightly with age

• no significantly elevated anti-dsDNA antibodies are found within the other immunoglobulin classes which differs from transgenic mice not homozygote for the Chuk^tm2Mka allele

homeostasis/metabolism

increased urine protein level ( J:113556 )

• about half of 8-month old mice have proteinuria in their urine at 30 mg/dl concentration

renal/urinary system

increased urine protein level ( J:113556 )

• about half of 8-month old mice have proteinuria in their urine at 30 mg/dl concentration

hematopoietic system

increased transitional stage B cell number ( J:113556 )

• numbers of T2 B cells are slightly enlarged in the spleen

decreased marginal zone B cell number ( J:113556 )

• marginal zone B cell numbers are reduced compared to controls

absent spleen marginal zone ( J:113556 )

• marginal zones could not be localized in these mice

abnormal B cell activation ( J:113556 )

• B cells have a strong response to T cell independent antigens producing higher levels of antigen-specific IgM, IgG2a, IgG2b class antibodies than wild-type controls

• however, there is no significant elevation of antigen-specific IgG1, IgG3, and IgA antibodies as is observed in transgenic mice on a wild-type background

• levels of antibodies produced are also lower than those in transgenic mice on a wild-type background

Genotype
MGI:3847938

cx4

• Allelic Composition: Chuk^tm2Mka/Chuk^tm2Mka; Tg(MMTV-CCND1)1Esmp/?
• Genetic Background: Not Specified

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:90978 )

N • the lactation defect observed in single Chuk mutants is completely suppressed by transgene expression and mice exhibit normal lobuloalveolar development