Mouse Genome Informatics
hm1
    Il6tm1Kopf/Il6tm1Kopf
B6.129S2-Il6tm1Kopf/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• the percentage of CD19+ B cell progenitors in the bone marrow is decreased from 58% to 35%
• after restimulation of spleen cells with keyhole limpet hemocyanin one week following immunization of mutant mice, reduced interferon gamma production is observed
• after restimulation of spleen cells with keyhole limpet hemocyanin one week following immunization of mutant mice, enhanced Il-4 secretion is observed
• intraperitoneal administration of LPS does not induce production of Il6 in the livers of mutants compared to wild-type where expression is increase
• mice treated with collagen II exhibit a lack of disease incident with normal joints compared with wild-type mice

homeostasis/metabolism
• injection of Il1beta results in body temperature elevation by about 0.5C (J:136166)
• inhibition of hepatic glucose production by ICV infusion of insulin is attenuated
• inhibition of hepatic glucose production assessed by a euglycemic hyperinsulinemic clamp is also attenuated
• decreased fasting glucagon levels on a high fat diet
• decreased fasting insulin levels on a high fat diet
• impaired glucose tolerance on a high fat diet

hematopoietic system
• the percentage of CD19+ B cell progenitors in the bone marrow is decreased from 58% to 35%

behavior/neurological
• increased latency to "give up" in a forced swim test
• significantly decreased time spent in the open arms of an elevated maze (J:96218)
• significantly decreased number of entries into the open arms of an elevated maze (J:96218)
• less time spent in the illuminated areas of a light-dark box (J:146951)
• lower latency to escape adverse stimuli
• fewer failures to escape adverse stimuli
• increased locomotor activity in open field tests
• increased time in non-REM sleep after sleep deprivation persists longer than for controls but increase in time is equivalent (J:105279)
• injection of Il1beta results in reduced dark phase wakefulness (J:136166)
• injection of Il1beta results in increased non REM sleep (J:136166)
• 30% increased time in REM sleep over a 24 hour period
• most extra REM sleep occurs in the light cycle
• length of REM bouts is normal but number of bouts increases

endocrine/exocrine glands
• alpha cell mass fails to increase on a high fat diet as it does in controls
• decreased fasting glucagon levels on a high fat diet
• decreased fasting insulin levels on a high fat diet

skeleton
• mice treated with collagen II exhibit a lack of disease incident with normal joints compared with wild-type mice


Mouse Genome Informatics
hm2
    Il6tm1Kopf/Il6tm1Kopf
involves: 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 60% mortality at day 12 after inoculation with C. rodentium

immune system
• mice challenged with Staphylococcus epidermidis cell-free supernatant exhibit impaired T cells (including CD4+, Th1, and Th17 cells) recruitment and production of IL17a compared with similarly treated wild-type mice
• mice challenged with Staphylococcus epidermidis cell-free supernatant exhibit fewer IL17a producing cells compared to in similarly treated wild-type mice
• following carrageenan induced inflammation, mice exhibit impaired neutrophil resolution after 7 days and delayed macrophage infiltration compared to in similarly treated wild-type mice
• 60% mortality at day 12 after inoculation with C. rodentium

homeostasis/metabolism
• at healing wounds, mice exhibit delayed re-epithelialization, formation of granulation tissue, macrophage infiltration, fibrin clearance, and vascularization compared with wild-type mice
• wounds become expanded beyond the boundaries of the original wound unlike in wild-type mice
• 24 hours after scalpel cortex injury, mice exhibit reduced microglial and astrocyte reaction compared with similarly treated wild-type mice (J:89814)
• following exposure to acid-induced acute lung injury, mice exhibit alleviated symptoms compared to wild-type mice (J:145306)

liver/biliary system
• modestly reduced oval cell response to a choline deficient diet and ethionine in the drinking water

nervous system
• 24 hours after scalpel cortex injury, mice exhibit reduced microglial and astrocyte reaction compared with similarly treated wild-type mice

hematopoietic system
• mice challenged with Staphylococcus epidermidis cell-free supernatant exhibit impaired T cells (including CD4+, Th1, and Th17 cells) recruitment and production of IL17a compared with similarly treated wild-type mice


Mouse Genome Informatics
hm3
    Il6tm1Kopf/Il6tm1Kopf
involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• lower body weight at 4 months of age is due largely to lower fat mass
• obesity develops by 8 months of age

immune system
• severe erosion of the intestinal epithelium from exposure to 3.5% dextran sodium sulfate
• T cells are reduced in the periphery by 20-40%
• thymocytes are consistently reduced by 20-40%
• modest increase in microglial density after haloperidol treatment relative to the increase seen in controls
• cytolytic activity of CD8 T cells to vaccinia virus infected cells is reduced 3-10 fold
• 100-fold reduction in SAA production by the liver in response to turpentine injection or listeria infection
• 10 to 100 fold increase in bacterial titers in the liver and spleen of mice infected with Listeria
• viral titers are 10-1000 fold higher in the ovaries and lungs of vaccinia virus infected mice

hematopoietic system
• T cells are reduced in the periphery by 20-40%
• thymocytes are consistently reduced by 20-40%
• modest increase in microglial density after haloperidol treatment relative to the increase seen in controls
• cytolytic activity of CD8 T cells to vaccinia virus infected cells is reduced 3-10 fold

cardiovascular system
• fewer capillaries in the heart
• loss of cell-cell interaction between myocytes and fibroblasts
• increased number of fibroblasts and decreased numbers of myocytes
• heart weight/body weight and heart weight/tibia length ratios both significantly reduced
• modestly increased interstitial collagen
• both anterior and posterior walls of the left ventricle are thin
• increased interstitial collagen in the free walls of both left and right ventricles
• increased cell proliferation and apoptosis in 5 day old hearts
• proliferation at 5 days primarily by non myocytes
• apoptosis at 5 days primarily of myocytes
• both fractional shortening and ejection fraction are decreased in adults and at 5 and 15 days of age
• cardiac dysfunction beginning at 15 days of age
• cardiac dilation is more or less normal at 5 days of age

behavior/neurological
• increased latency to float in a forced swimming test
• reduced despair behavior
• more time in the closed arms of an elevated + maze after forced swimming tests
• reduced exploration in initial phase of novel object recognition tests (J:147420)
• increased exploration in novel object recognition tests (J:148881)
• reduced object recognition when retested (J:147420)
• greater object recognition memory (J:148881)
• longer escape latencies in a Morris water maze
• shorter time spent in the target quadrant of a Morris water maze
• slower to relocate platform after it is moved

nervous system
• parvalbumin positive interneurons in the hippocampus suffer less loss in numbers with age
• modest increase in microglial density after haloperidol treatment relative to the increase seen in controls
• density fails to increase in response to neurotoxin (6-OHDA) lesioning
• axon terminal tree is 25% larger in the substantia nigra pars compacta than for controls
• resistant to the effects of haloperidol treatment on terminal trees
• neurotoxin lesion results in reduced terminal tree density
• age induced increase in oxygen consumption in synaptosomes is attenuated

muscle
• both fractional shortening and ejection fraction are decreased in adults and at 5 and 15 days of age
• cardiac dysfunction beginning at 15 days of age
• cardiac dilation is more or less normal at 5 days of age
• migration of primary myoblasts is reduced relative to controls
• cross-sectional area of myofibers does not increase after overload of the plantaris muscle by incapacitation of the gastrocnemius, measured 14 and 42 days after overload
• no change in myonuclear numbers

vision/eye
• higher level of apoptosis after retinal separation from the retinal pigment epithelium
• higher rate of photoreceptor cell death after 1 month

skeleton
• callus formed after bone fracture is denser after 2 weeks than is true in controls
• tissue mineral density is less at 4 and 6 weeks after injury than for controls
• greater collagen content at 2 weeks after fracture but not at 4 or 6 weeks
• mineral density of cortical bone reduced
• reduced crystallinity relative to controls
• reduced mineral/matrix ratio in cortical bone at both 2 and 4 weeks

tumorigenesis
• reduced incidence of hepatocellular cancer in males treated with diethyl nitrosamine relative to incidence in control males

liver/biliary system
• less necrosis resulting from diethyl nitrosamine treatment
• less hepatic injury in males from treatment with diethyl nitrosamine
• less apoptosis due to diethyl nitrosamine treatment
• less compensatory proliferation as a result of diethyl nitrosamine treatment

respiratory system
• elevated respiratory exchange rate in young mice

homeostasis/metabolism
• elevated basal glucose levels at 8 months but not in younger mice
• glucose levels do not differ from controls in young mice after 1 hour of exercise
• oxygen consumption is not maintained at as high a level after 12 minutes of running as in controls
• 100-fold reduction in SAA production by the liver in response to turpentine injection or listeria infection
• reduced treadmill endurance
• reduced incidence of hepatocellular cancer in males treated with diethyl nitrosamine relative to incidence in control males
• callus formed after bone fracture is denser after 2 weeks than is true in controls
• tissue mineral density is less at 4 and 6 weeks after injury than for controls
• greater collagen content at 2 weeks after fracture but not at 4 or 6 weeks

endocrine/exocrine glands
• develops more slowly (J:125449)

digestive/alimentary system
• severe erosion of the intestinal epithelium from exposure to 3.5% dextran sodium sulfate

integument
• develops more slowly (J:125449)

cellular
• migration of primary myoblasts is reduced relative to controls


Mouse Genome Informatics
hm4
    Il6tm1Kopf/Il6tm1Kopf
involves: 129S2/SvPas * C57BL/6J * CE/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• a substantial proportion of homozygotes develop generalized seizures after 250 days of age

nervous system
• a substantial proportion of homozygotes develop generalized seizures after 250 days of age


Mouse Genome Informatics
cn5
    Il6tm1Kopf/Il6tm1Kopf
Junbtm3Wag/Junbtm3Wag
Tg(KRT5-cre)1Tak/0

involves: 129/Sv * 129P2/OlaHsd * 129S2/SvPas * C3H * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• mice exhibit normal lifespan unlike Junbtm3Wag/Junbtm3Wag Tg(KRT5-cre)1Tak mice (J:155575)

immune system
N
• mice exhibit a rescue of the systemic lupus erythematosus associated phenotypes observed in Junbtm3Wag/Junbtm3Wag Tg(KRT5-cre)1Tak mice including normal lymph node architecture, plasma cell count, and antinuclear autoantibodies (J:155575)

renal/urinary system
N
• mice exhibit a rescue of the lupus associated kidney phenotypes observed in Junbtm3Wag/Junbtm3Wag Tg(KRT5-cre)1Tak mice (J:155575)

homeostasis/metabolism
N
• ce exhibit normal urine albumin levels unlike in Junbtm3Wag/Junbtm3Wag Tg(KRT5-cre)1Tak mice (J:155575)

integument
N
• mice exhibit a rescue of the lupus associated skin phenotypes observed in Junbtm3Wag/Junbtm3Wag Tg(KRT5-cre)1Tak mice (J:155575)
• milder than in Junbtm3Wag/Junbtm3Wag Tg(KRT5-cre)1Tak mice


Mouse Genome Informatics
cn6
    Il6tm1Kopf/Il6+
Prdm1tm1Clme/Prdm1tm1Clme
Tg(Itgax-cre)1-1Reiz/0

involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• mice do not develop autoantibodies, they mount an antibody response indistinguishable from control mice to NP-CGG, dendritic cells express the same level of IL-6 as dendritic cells from control mice after LPS stimulation, and show normal levels of follicular T helper cells and germinal cells in the spleen (J:178876)


Mouse Genome Informatics
cx7
    Ash1lTn(pb-Act-RFP)1.AF0-180T25Zhu/Ash1lTn(pb-Act-RFP)1.AF0-180T25Zhu
Il6tm1Kopf/Il6tm1Kopf

B6.Cg-Ash1lTn(pb-Act-RFP)1.AF0-180T25Zhu Il6tm1Kopf
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• reduced inflammation compared with Ash1lTn(pb-Act-RFP)1.AF0-180T25Zhu homozygotes
• compared with Il6tm1Kopf homozygotes

skeleton
• compared with Il6tm1Kopf homozygotes


Mouse Genome Informatics
cx8
    Il6tm1Kopf/Il6tm1Kopf
Tg(ED-L2-IL1RN/IL1B)#Tcw/?

B6.Cg-Il6tm1Kopf Tg(ED-L2-IL1RN/IL1B)#Tcw
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
N
• absence of Il6 expression completely abolishes the metaplastic and dysplastic phenotypes seen in transgenic mice expressing Il6 (J:180282)
• minor inflammatory response

immune system
• minor inflammatory response

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Barrett Esophagus 614266 J:180282


Mouse Genome Informatics
cx9
    Il6tm1Kopf/Il6+
Tg(ED-L2-IL1RN/IL1B)#Tcw/?

B6.Cg-Il6tm1Kopf Tg(ED-L2-IL1RN/IL1B)#Tcw
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
N
• reduced of Il6 expression completely decreases metaplasia and abolishes dysplasia (J:180282)

immune system


Mouse Genome Informatics
cx10
    Il6tm1Kopf/Il6tm1Kopf
Inpp5dtm1Rkh/Inpp5dtm1Rkh

involves: 129 * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• the percentage of prolymphocyte in the bone marrow is slightly less than wild-type (35% versus 27%)
• the percentage of CD19+ B cell progenitors in the bone marrow is decreased by almost 4-fold
• 78% of mutant bone marrow cells are Mac-1+ compared to 56% in wild-type

hematopoietic system
• the percentage of prolymphocyte in the bone marrow is slightly less than wild-type (35% versus 27%)
• the percentage of CD19+ B cell progenitors in the bone marrow is decreased by almost 4-fold
• 78% of mutant bone marrow cells are Mac-1+ compared to 56% in wild-type
• there is a 2-fold decrease in Lin-c-KitloSca-1lo population in the bone marrow that contains the hematopoietic stem cell population


Mouse Genome Informatics
cx11
    Il6tm1Kopf/Il6tm1Kopf
Tanktm1Aki/Tanktm1Aki

involves: 129/Sv * 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• the glomerulonephritis and the auto-antibodies that occur in Tank-null mice do not occur on a IL-6 deficient background (J:151757)


Mouse Genome Informatics
cx12
    Il11ra1tm1Wehi/Il11ra1tm1Wehi
Il6tm1Kopf/Il6tm1Kopf

involves: 129/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
• adult double homozygotes do NOT develop spontaneous gastric hyperplasia or gastric adenomas
• however, double homozygotes exhibit enhanced colitis in response to DSS-mediated intestinal injury, as shown by increased inflammation, crypt damage, severe weight loss, and increased morbidity relative to wild-type or Il11ra1tm1Wehi mice

immune system
• adult double homozygotes do NOT develop spontaneous gastric hyperplasia or gastric adenomas
• however, double homozygotes exhibit enhanced colitis in response to DSS-mediated intestinal injury, as shown by increased inflammation, crypt damage, severe weight loss, and increased morbidity relative to wild-type or Il11ra1tm1Wehi mice


Mouse Genome Informatics
cx13
    Il6tm1Kopf/Il6tm1Kopf
Il6sttm1Ern/Il6sttm1Ern

involves: 129S1/Sv * 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• neutrophil infiltration of the peritoneal cavity and subsequent clearance in induced inflammation normal (J:139226)
• mice are resistant to LPS-induced shock


Mouse Genome Informatics
cx14
    Il6tm1Kopf/Il6tm1Kopf
Liftm1Stw/Liftm1Stw

involves: 129S1/Sv * 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• 24 hours after scalpel cortex injury, mice exhibit reduced microglial and astrocyte reaction compared with similarly treated wild-type mice but similar to in single homozygotes

nervous system
• 24 hours after scalpel cortex injury, mice exhibit reduced microglial and astrocyte reaction compared with similarly treated wild-type mice but similar to in single homozygotes


Mouse Genome Informatics
cx15
    Ctsctm1Ley/Ctsctm1Ley
Il6tm1Kopf/Il6tm1Kopf

involves: 129S2/SvPas * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• survival of experimentally induced sepsis is similar to that of controls (J:88160)


Mouse Genome Informatics
cx16
    Il6tm1Kopf/Il6tm1Kopf
Npc1m1N/Npc1m1N

involves: 129S2/SvPas * BALB/c * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• nmber of activated microglial and astroglial cells is decreased in 6-week old mice compared to Il6-sufficient, Npc1-null mice


Mouse Genome Informatics
cx17
    Il6tm1Kopf/Il6+
Ncoa5tm1Hxia/Ncoa5+

involves: 129S2/SvPas * BALB/c * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
N
• unlike Ncoa5tm1Hxia male heterozygotes, male mice exhibit normal circulating glucose levels and improved glucose tolerance (J:207622)


Mouse Genome Informatics
cx18
    Il6tm1Kopf/Il6tm1Kopf
Tg(Rorc-EGFP)1Ebe/?

involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• splenic Th-17 cells that have alphabeta TCR and are GFP-positive are decreased by half compared to controls
• the ratio of IL-17 producing cells to IL-10 producing cells among the GFP-positive T cell population is significantly decreased
• numbers of Th17 gammadelta T cells are normal

immune system
• splenic Th-17 cells that have alphabeta TCR and are GFP-positive are decreased by half compared to controls
• the ratio of IL-17 producing cells to IL-10 producing cells among the GFP-positive T cell population is significantly decreased
• numbers of Th17 gammadelta T cells are normal


Mouse Genome Informatics
cx19
    Foxp3tm1Kuch/?
Il6tm1Kopf/Il6tm1Kopf

involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• numbers of FoxP3+ T cells are increased in MOG-immunized mice compared to immunized controls
• the ratio of MOG-specific Treg to effector T cells is reversed compared to controls
• immunization with MOG-peptide leads to less differentiation of Th17 effector cells
• when Treg cells are depleted, Th17 T cells form upon MOG immunization
• na´ve T cells can be differentiated in vitro to Th17 T cells by incubating with Tgf-beta plus IL-21 albeit to a lesser degree than controls

homeostasis/metabolism
• mice were confirmed not to produce IL-6

immune system
• numbers of FoxP3+ T cells are increased in MOG-immunized mice compared to immunized controls
• the ratio of MOG-specific Treg to effector T cells is reversed compared to controls
• immunization with MOG-peptide leads to less differentiation of Th17 effector cells
• when Treg cells are depleted, Th17 T cells form upon MOG immunization
• na´ve T cells can be differentiated in vitro to Th17 T cells by incubating with Tgf-beta plus IL-21 albeit to a lesser degree than controls
• mice were confirmed not to produce IL-6
• less IL-17 is secreted when T cells from MOG-challenged mice are presented MOG peptide in vitro
• mice are resistant to EAE induced by immunization with MOG-peptide


Mouse Genome Informatics
cx20
    ApcMin/Apc+
Il6tm1Kopf/Il6tm1Kopf

involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
N
• no gastrocnemius muscle wasting (J:130429)

adipose tissue
N
• normal epididymal fat pads (J:130429)

tumorigenesis
• numbers of gastrointestinal polyps 32% lower at 26 weeks than when both Il6 alleles are wild-type
• polyp sizes are reduced


Mouse Genome Informatics
cx21
    Il6tm1Kopf/Il6+
Ncoa5tm1Hxia/Ncoa5+

involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
N
• Ncoa5tm1Hxia male heterozygotes, male mice are fertile (J:207622)

tumorigenesis
• fewer and smaller maximum tumor volume than in Ncoa5tm1Hxia male heterozygotes (J:207622)

homeostasis/metabolism
N
• unlike Ncoa5tm1Hxia male heterozygotes, male mice exhibit normal circulating glucose levels, glucose tolerance and insulin sensitivity (J:207622)


Mouse Genome Informatics
cx22
    Il6tm1Kopf/Il6+
Ncoa5tm1Hxia/Ncoa5tm1Hxia

involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• no mice are produced from fertile double heterozygotes


Mouse Genome Informatics
cx23
    Il6tm1Kopf/Il6tm1Kopf
Il6ratm1.2Drew/Il6ratm1.2Drew

involves: 129S2/SvPas * C57BL/6 * C57BL/6N * FVB/N * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• mice exhibit delayed re-epithelialization of small and large wounds is delayed compared to in wild-type mice
• mice exhibit deficits in the formation of granulation tissue at wounds compared with wild-type mice
• however, macroscopic wound closure rates are normal


Mouse Genome Informatics
cx24
    Galctwi/Galctwi
Il6tm1Kopf/Il6tm1Kopf

involves: 129S2/SvPas * C57BL/6J * CE/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• the average onset of twitching is earlier in double homozygotes than mice homozygous only for twitcher (22.2 days of age versus 25.9 days of age respectively), although lifespan, body weight and frequency of twitching do not differ significantly

nervous system
• leakage of the blood-brain barrier is detected in the cerebrum, hindbrain, and cervical spinal cord as detected by horseradish peroxidase tail vein injection, and immunoglobulin and albumin immunohistochemistry
• lipopolysaccharide injection greatly enhances the blood-brain barrier disruption leading to death
• the deep cerebellar white matter shows a significant increase in periodic acid-Schiff staining cells and a trend toward increased lectin-positive cells relative to mice homozygous only for twitcher
• more exaggerated gliosis is found around some vessels and pial surfaces in the double mutants than in mice homozygous only for twitcher

cardiovascular system
• leakage of the blood-brain barrier is detected in the cerebrum, hindbrain, and cervical spinal cord as detected by horseradish peroxidase tail vein injection, and immunoglobulin and albumin immunohistochemistry
• lipopolysaccharide injection greatly enhances the blood-brain barrier disruption leading to death

homeostasis/metabolism
• hindbrain has TNF levels elevated above that found in mice homozygous only for twitcher and mice homozygous only for twitcher have significantly elevated TNF levels in hindbrain

immune system
• hindbrain has TNF levels elevated above that found in mice homozygous only for twitcher and mice homozygous only for twitcher have significantly elevated TNF levels in hindbrain