mortality/aging
|
• fewer than expected mice are present at weaning
|
|
• fewer than expected mice are present between E12.5 and E18.5
|
cardiovascular system
|
• i.v. injected FITC-dextran is mostly retained within the vasculature at levels similar to those in wild-type controls
(J:253134)
• mice exhibit normal mean arterial blood pressure (MAP) and heart rate under normal conditions
(J:275252)
|
|
• mice with bleeding exhibit dilated ventral skin blood vessels with poor mural cell coverage compared with wild-type mice
|
|
• mice with bleeding exhibit dilated ventral skin blood vessels with poor mural cell coverage compared with wild-type mice
|
|
• mice with bleeding exhibit dilated ventral skin blood vessels with poor mural cell coverage compared with wild-type mice
|
|
• in some mice
|
hemorrhage
(
J:167262
)
|
• at E14.5, some mice exhibit subcutaneous hemorrhage unlike wild-type mice
• at E18.5, some mice exhibit hemorrhage in the neck, head, limbs, and other areas of the body unlike wild-type mice
• at E18.5, some mice exhibit hemorrhagic lesions in pericardial cavities, periocular tissues, salivary glands, and subcutaneous tissues unlike wild-type mice
• however, blood coagulation is normal
|
|
• at E18.5, 4 of 17 mice exhibit thymic hemorrhage unlike wild-type mice
|
|
• in 14 of 17 mice at E18.5
|
|
• in 1 of 17 mice at E18.5
|
|
• after i.v. injection of lysophosphatidic acid (18:1-LPA), mice show attenuated LPA-induced transient hypertension with a slightly but significantly lower response to various LPA dosages than in similarly treated wild-type controls
• however, mice exhibit normal hypertensive responses to phenylephrine and norepinephrine
|
homeostasis/metabolism
|
• high endothelial venules (HEVs) and fibroblastic reticular cells show normal expression of ENPP2/ATX (ectonucleotide pyrophosphatase/phosphodiesterase 2, also known as autotaxin), indicating normal local production of lysophosphatidic acid (LPA)
|
|
• some mice exhibit effusions in the body surface unlike wild-type mice
|
|
• in some mice
|
|
• in 14 of 17 mice at E18.5
|
skin edema
(
J:167262
)
|
• in some mice at E14.5 and E18.5
|
growth/size/body
|
• some mice at E10.5 and E12.5
|
omphalocele
(
J:167262
)
|
• in some mice at E18.5
|
|
• some mice at E14.5
|
embryo
|
• at E12.5, one third of mice exhibit various developmental anomalies unlike wild-type mice
|
|
• some mice at E10.5 and E12.5
|
skeleton
|
• in some mice at E18.5
|
craniofacial
|
• in some mice at E18.5
|
integument
|
• mice with bleeding exhibit dilated ventral skin blood vessels with poor mural cell coverage compared with wild-type mice
|
skin edema
(
J:167262
)
|
• in some mice at E14.5 and E18.5
|
muscle
|
• mice with bleeding exhibit dilated ventral skin blood vessels with poor mural cell coverage compared with wild-type mice
|
respiratory system
|
• in 1 of 17 mice at E18.5
|
immune system
|
• mice show normal formation of high endothelial venules (HEVs), B-cell follicles, and T-cell areas in the lymph nodes (LNs), with no abnormalities in CD4, CD8 or B220 expression
• overall tissue architecture and blood vessel distribution pattern is normal in peripheral LNs
|
|
• mice show a significantly greater lymphocyte accumulation within the HEV endothelial cell (EC) layer of the inguinal LN (ILN) than Lpar4tm1Sati heterozygotes and wild-type controls
• increased lymphocyte accumulation is also noted within the EC layer of PNAd+ HEV ECs in the mesenteric LN (MLN), but to a lesser extent than in the PNAd+ HEV ECs of peripheral LNs
• TEM analysis of HEVs in the ILNs shows more lymphocytes in the HEV EC layer including the perivenular channels, occasionally causing narrowing of the luminal surface of HEV ECs
• most accumulated lymphocytes are nested between the ECs and the underlying basal lamina
• most pockets in the HEV EC layer (areas where lymphocytes reside for several minutes before they enter the LN parenchyma) contain more lymphocytes (occasionally >10 in a single pocket), whereas wild-type pockets typically house up to 4-5 lymphocytes
• after adoptive transfer, the number of migrated wild-type GFP+ donor cells is mildly reduced in the ILN, but not in spleen, with T-cell migration more strongly affected than B-cell migration in the ILN
• in a trafficking assay using whole-mount analysis of LNs, the density of transferred lymphocytes around HEVs (= number of donor cells within the HEV EC layer / number of recently extravasated cells) as well as the HEV surface area and volume are significantly increased, indicating delayed lymphocyte transmigration across the HEV wall
|
|
• lymph sacs and lymphatic vessels are dilated compared to in wild-type mice
• however, lymphatic endothelial cell proliferation is normal
|
hematopoietic system
|
• mice show a significantly greater lymphocyte accumulation within the HEV endothelial cell (EC) layer of the inguinal LN (ILN) than Lpar4tm1Sati heterozygotes and wild-type controls
• increased lymphocyte accumulation is also noted within the EC layer of PNAd+ HEV ECs in the mesenteric LN (MLN), but to a lesser extent than in the PNAd+ HEV ECs of peripheral LNs
• TEM analysis of HEVs in the ILNs shows more lymphocytes in the HEV EC layer including the perivenular channels, occasionally causing narrowing of the luminal surface of HEV ECs
• most accumulated lymphocytes are nested between the ECs and the underlying basal lamina
• most pockets in the HEV EC layer (areas where lymphocytes reside for several minutes before they enter the LN parenchyma) contain more lymphocytes (occasionally >10 in a single pocket), whereas wild-type pockets typically house up to 4-5 lymphocytes
• after adoptive transfer, the number of migrated wild-type GFP+ donor cells is mildly reduced in the ILN, but not in spleen, with T-cell migration more strongly affected than B-cell migration in the ILN
• in a trafficking assay using whole-mount analysis of LNs, the density of transferred lymphocytes around HEVs (= number of donor cells within the HEV EC layer / number of recently extravasated cells) as well as the HEV surface area and volume are significantly increased, indicating delayed lymphocyte transmigration across the HEV wall
|
cellular
|
• mice show a significantly greater lymphocyte accumulation within the HEV endothelial cell (EC) layer of the inguinal LN (ILN) than Lpar4tm1Sati heterozygotes and wild-type controls
• increased lymphocyte accumulation is also noted within the EC layer of PNAd+ HEV ECs in the mesenteric LN (MLN), but to a lesser extent than in the PNAd+ HEV ECs of peripheral LNs
• TEM analysis of HEVs in the ILNs shows more lymphocytes in the HEV EC layer including the perivenular channels, occasionally causing narrowing of the luminal surface of HEV ECs
• most accumulated lymphocytes are nested between the ECs and the underlying basal lamina
• most pockets in the HEV EC layer (areas where lymphocytes reside for several minutes before they enter the LN parenchyma) contain more lymphocytes (occasionally >10 in a single pocket), whereas wild-type pockets typically house up to 4-5 lymphocytes
• after adoptive transfer, the number of migrated wild-type GFP+ donor cells is mildly reduced in the ILN, but not in spleen, with T-cell migration more strongly affected than B-cell migration in the ILN
• in a trafficking assay using whole-mount analysis of LNs, the density of transferred lymphocytes around HEVs (= number of donor cells within the HEV EC layer / number of recently extravasated cells) as well as the HEV surface area and volume are significantly increased, indicating delayed lymphocyte transmigration across the HEV wall
|