All Phenotypes Lyz2<em1(icre)Gpt> MGI Mouse

Phenotypes associated with this allele

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

cardiovascular system

decreased susceptibility to atherosclerosis ( J:357567 )

• mice fed a high fat diet (HFD) for 12 weeks show a significant reduction in lipid content, necrotic core, atherosclerotic plaque area and mRNA expression of Itgam (integrin alpha M, aka Cd11b) in the plaque, but greater aortic collagen content than HFD-fed mice homozygous only for Apoe^em1Gpt and Slc16a3^em1Gpt, suggesting a delay in atherosclerosis progression

• arteries of HFD-fed mice show a further elevation of the lactylation modifier EP300 (E1A binding protein p300), pan-lysine lactylation (Pan Kla), and H3 lysine 18 lactylation (H3K18la) with increased macrophage H3K18la in the aortic root relative to HFD-fed mice only homozygous for Apoe^em1Gpt and Slc16a3^em1Gpt

• arteries from HFD-fed mice show decreased mRNA expression of proinflammatory genes (Il6, Il1b, Tnf) and increased mRNA expression of anti-inflammatory genes (Arg1, Il10, Tgfb1) relative to arteries from HFD-fed mice only homozygous for Apoe^em1Gpt and Slc16a3^em1Gpt

increased susceptibility to atherosclerosis ( J:357567 )

• after treatment with C646 (an EP300 inhibitor), HFD-fed mice show a significant increase in atherosclerotic plaque area along with a reduction in the expression of H3K18la and of reparative genes (Arg1, Il10, Mrc1, Tgfb1, Pdha1, Idh2, Sdha, and Fh1) relative to vehicle-treated HFD-fed controls

immune system

abnormal macrophage physiology ( J:357567 )

• bone marrow-derived macrophages (BMDMs) from HFD-fed mice show increased cellular oxygen consumption rate (OCR) and decreased extracellular acidification rate (ECAR) relative to BMDMs from HFD-fed mice only homozygous for Apoe^em1Gpt and Slc16a3^em1Gpt

increased circulating interleukin-10 level ( J:357567 )

• HFD-fed mice show significantly higher serum IL-10 levels than HFD-fed mice only homozygous for Apoe^em1Gpt and Slc16a3^em1Gpt

decreased circulating interleukin-6 level ( J:357567 )

• HFD-fed mice show significantly lower serum IL-6 levels than HFD-fed mice only homozygous for Apoe^em1Gpt and Slc16a3^em1Gpt

decreased circulating tumor necrosis factor level ( J:357567 )

• HFD-fed mice show significantly lower serum TNF-alpha levels than HFD-fed mice only homozygous for Apoe^em1Gpt and Slc16a3^em1Gpt

cellular

abnormal aerobic respiration ( J:357567 )

• arteries from HFD-fed mice show decreased mRNA expression of glycolysis genes (Hk2 and Ldha) relative to arteries from HFD-fed mice only homozygous for Apoe^em1Gpt and Slc16a3^em1Gpt

abnormal epigenetic regulation of gene expression ( J:357567 )

• BMDMs from HFD-fed mice show a significant increase in the enrichment of H3 lysine 18 lactylation (H3K18la) at the promoters of reparative genes, including anti-inflammatory genes and TCA cycle genes (Arg1, Il10, Mrc1, Tgfb1, Pdha1, Idh2, Sdha, and Fh1) relative to BMDMs from HFD-fed mice only homozygous for Apoe^em1Gpt and Slc16a3^em1Gpt

• after treatment with C646 (an EP300 inhibitor), BMDMs from HFD-fed mice show a significant reduction in the enrichment of H3K18la at macrophage reparative gene promoters

abnormal mitochondrial physiology ( J:357567 )

• BMDMs from HFD-fed mice show increased cellular oxygen consumption rate (OCR) and decreased extracellular acidification rate (ECAR) relative to BMDMs from HFD-fed mice only homozygous for Apoe^em1Gpt and Slc16a3^em1Gpt

• moreover, arteries from HFD-fed mice show decreased mRNA expression of glycolysis genes and increased mRNA expression of tricarboxylic acid (TCA) cycle genes, suggesting improved mitochondria function

abnormal tricarboxylic acid cycle ( J:357567 )

• arteries from HFD-fed mice show increased mRNA expression of tricarboxylic acid (TCA) cycle genes (Pdha1, Idh2, Sdha, and Fh1) relative to arteries from HFD-fed mice only homozygous for Apoe^em1Gpt and Slc16a3^em1Gpt

homeostasis/metabolism

increased circulating interleukin-10 level ( J:357567 )

• HFD-fed mice show significantly higher serum IL-10 levels than HFD-fed mice only homozygous for Apoe^em1Gpt and Slc16a3^em1Gpt

decreased circulating interleukin-6 level ( J:357567 )

• HFD-fed mice show significantly lower serum IL-6 levels than HFD-fed mice only homozygous for Apoe^em1Gpt and Slc16a3^em1Gpt

decreased circulating tumor necrosis factor level ( J:357567 )

• HFD-fed mice show significantly lower serum TNF-alpha levels than HFD-fed mice only homozygous for Apoe^em1Gpt and Slc16a3^em1Gpt

increased transforming growth factor beta level ( J:357567 )

• HFD-fed mice show significantly higher serum TGF-beta levels than HFD-fed mice only homozygous for Apoe^em1Gpt and Slc16a3^em1Gpt

hematopoietic system

abnormal macrophage physiology ( J:357567 )

Allelic Composition	Arih1^em3Gpt/Arih1^em3Gpt Lyz2^em1(icre)Gpt/Lyz2⁺
Genetic Background	C57BL/6JGpt-Arih1^em3Gpt Lyz2^em1(icre)Gpt

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Arih1^em3Gpt mutation (0 available); any Arih1 mutation (32 available)
Lyz2^em1(icre)Gpt mutation (0 available); any Lyz2 mutation (40 available)

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

mortality/aging

increased susceptibility to Herpesvirales infection induced morbidity/mortality ( J:330879 )

immune system

immune system phenotype ( J:330879 )

N	• in vitro differentiation of bone marrow derived dendritic cells and bone marrow derived macrophages is normal

decreased circulating interferon-beta level ( J:330879 )

• in HSV-1-infected mice

decreased circulating interleukin-6 level ( J:330879 )

• in HSV-1-infected mice

decreased interferon-beta secretion ( J:330879 )

• in bone marrow derived dendritic cells exposed to HSV-1 or cytoplasmic DNA

• however, bone marrow derived dendritic cells exhibit normal production of IFN-beta in response to SeV-, poly(I:C)-, or cGAMP

decreased interleukin-6 secretion ( J:330879 )

• in bone marrow derived dendritic cells exposed to HSV-1 or cytoplasmic DNA

• however, bone marrow derived dendritic cells exhibit normal production of IL6 in response to SeV-, poly(I:C)-, or cGAMP

increased susceptibility to Herpesvirales infection ( J:330879 )

• bone marrow derived dendritic cells exposed to HSV-1 or cytoplasmic DNA produce less IFN-beta and IL6

• HSV-1-infected mice exhibit increased viral titer in the brain, decreased IFN-beta and IL6 sera levels, and increased mortality compared with control mice

• however, bone marrow derived dendritic cells exhibit normal production of IFN-beta and IL6 in response to SeV-, poly(I:C)-, or cGAMP

increased susceptibility to Herpesvirales infection induced morbidity/mortality ( J:330879 )

homeostasis/metabolism

decreased circulating interferon-beta level ( J:330879 )

• in HSV-1-infected mice

decreased circulating interleukin-6 level ( J:330879 )

• in HSV-1-infected mice

Allelic Composition	Arih1^em3Gpt/Arih1^em3Gpt Lyz2^em1(icre)Gpt/Lyz2⁺ Trex1^em1Gpt/Trex1^em1Gpt
Genetic Background	C57BL/6JGpt-Arih1^em3Gpt Trex1^em1Gpt Lyz2^em1(icre)Gpt

Find Mice

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

mortality/aging

mortality/aging ( J:330879 )

N	• unlike Trex1^em1Gpt homozygotes, mice exhibit normal survival

immune system

immune system phenotype ( J:330879 )

N	• unlike Trex1^em1Gpt homozygotes, mice exhibit normalized spleen size and weight; serum levels of TNF, CXCL1, CCL5, and total IgG; and autoimmune phenotypes

growth/size/body

growth/size/body region phenotype ( J:330879 )

N	• unlike Trex1^em1Gpt homozygotes, mice exhibit normalized development and body weight

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