Phenotypes associated with this allele

• Allele Symbol: Lgals3^tm1Ftl
• Allele Name: targeted mutation 1, Fu-Tong Liu
• Allele ID: MGI:2386938
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lgals3^tm1Ftl/Lgals3^tm1Ftl	B6.129S2-Lgals3^tm1Ftl	MGI:3629701
hm2	Lgals3^tm1Ftl/Lgals3^tm1Ftl	involves: 129S2/SvPas * C57BL/6	MGI:3629708
hm3	Lgals3^tm1Ftl/Lgals3^tm1Ftl	involves: 129S2/SvPas * CD-1	MGI:5637814
cx4	Cys1^cpk/Cys1^cpk Lgals3^tm1Ftl/Lgals3^tm1Ftl	B6.Cg-Cys1^cpk Lgals3^tm1Ftl	MGI:3789178
cx5	Cys1^cpk/Cys1^cpk Lgals3^tm1Ftl/Lgals3^tm1Ftl	involves: 129/Sv * C57BL/6	MGI:3789176

Genotype
MGI:3629701

hm1

• Allelic Composition: Lgals3^tm1Ftl/Lgals3^tm1Ftl
• Genetic Background: B6.129S2-Lgals3^tm1Ftl

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

immune system

small intestinal inflammation ( J:109126 )

• mild leukocytic infiltration is seen in the small intestine compared to wild-type 6 days after infection

decreased macrophage cell number ( J:109126 )

• on days 14 and 28 there are many fewer infiltrating macrophages in the brain compared to controls

abnormal CD8-positive, alpha-beta cytotoxic T cell morphology ( J:109126 )

• there is a reduction in CD8 T cells in the brain on day 28 compared to controls

increased IgG level ( J:109126 )

• mutants show a higher IgG2a to IgG1 ratio than controls

abnormal dendritic cell physiology ( J:109126 )

• after infection with T. gondii, mutant dendritic cells produces excess Il12p40

abnormal interferon secretion ( J:109126 )

• levels are higher in mutant sera after infection

• levels of Ifng released from mutant splenocytes are higher up to day 14

increased interleukin-12b secretion ( J:109126 )

• levels of Il12p40 are higher in mutant sera after infection

• higher amounts of Il12p40 are released by Lgals-deficient splenocytes even without stimulation

brain inflammation ( J:109126 )

• inflammation seen in mutant brains is lower than in controls during the first 21 days of oral infection but by day 28, inflammation is comparable with that in controls

• after intraperitoneal infection, brains of mutants show 5-fold higher numbers of cysts compared to controls

lung inflammation ( J:109126 )

• after initial 2 weeks post-infection, inflammation decreased in controls but persisted in mutant mice

• 4 days after intraperitoneal infection, mutants show a lower incidence of infiltrates containing neutrophils and macrophages

abnormal response to infection ( J:109126 )

• in Lgals-deficient mice, no necrotic lesions of the villi in the small intestine are seen unlike in wild-type controls 8 days after oral infection; more pulmonary infiltrates are seen on day 21 in mutants

• parasitic burden in lungs of null mice is much higher than in controls on day7 after oral infection; tissue parasitism is higher in nulls on day14, but sharply declines on day 21

• in brains of null mice on day14, number of cysts in 11x higher than in controls after oral infection; this decreased to 6x on day 21 and 3x on day28

increased susceptibility to parasitic infection ( J:109126 )

• Lgals-deficient mice show lower survival rates when infected intraperitoneally with T. gondii

hematopoietic system

decreased macrophage cell number ( J:109126 )

• on days 14 and 28 there are many fewer infiltrating macrophages in the brain compared to controls

abnormal CD8-positive, alpha-beta cytotoxic T cell morphology ( J:109126 )

• there is a reduction in CD8 T cells in the brain on day 28 compared to controls

increased IgG level ( J:109126 )

• mutants show a higher IgG2a to IgG1 ratio than controls

nervous system

brain inflammation ( J:109126 )

• inflammation seen in mutant brains is lower than in controls during the first 21 days of oral infection but by day 28, inflammation is comparable with that in controls

• after intraperitoneal infection, brains of mutants show 5-fold higher numbers of cysts compared to controls

digestive/alimentary system

small intestinal inflammation ( J:109126 )

• mild leukocytic infiltration is seen in the small intestine compared to wild-type 6 days after infection

respiratory system

lung inflammation ( J:109126 )

• after initial 2 weeks post-infection, inflammation decreased in controls but persisted in mutant mice

• 4 days after intraperitoneal infection, mutants show a lower incidence of infiltrates containing neutrophils and macrophages

Genotype
MGI:3629708

hm2

• Allelic Composition: Lgals3^tm1Ftl/Lgals3^tm1Ftl
• Genetic Background: involves: 129S2/SvPas * C57BL/6

immune system

peritoneal inflammation ( J:60741 )

• Lgals-deficient mice display attenuated peritoneal inflammation compared to wild-type upon stimulation with thioglycollate broth administration

increased eosinophil cell number ( J:60741 )

• mutants show a higher percentage of eosinophils on days 1, 2 and 4 after thioglycollate broth treatment

decreased lymphocyte cell number ( J:60741 )

• null mice have lower numbers of lymphocytes on days 2 and 4 after treatment

decreased macrophage cell number ( J:60741 , J:313172 )

♂ • the % of testicular macrophages within the population of CD45+ leukocytes is reduced by 11% in adult males (J:313172)

abnormal monocyte morphology ( J:60741 )

• on day 1 after treatment mutants have a lower percentage of monocytes/macrophages

decreased monocyte cell number ( J:60741 )

abnormal leukocyte physiology ( J:60741 )

• leukocytes from mutants show weaker NF-kappa b binding activity upon stimulation with thioglycollate broth than wild-type controls

abnormal macrophage physiology ( J:60741 )

• peritoneal macrophages show decreased areas of adherence in culture compared to wild-type

increased macrophage apoptosis ( J:60741 )

• Lgals-deficient macrophages are more sensitive to apoptotic stimuli in culture

hematopoietic system

increased eosinophil cell number ( J:60741 )

• mutants show a higher percentage of eosinophils on days 1, 2 and 4 after thioglycollate broth treatment

decreased lymphocyte cell number ( J:60741 )

• null mice have lower numbers of lymphocytes on days 2 and 4 after treatment

decreased macrophage cell number ( J:60741 , J:313172 )

♂ • the % of testicular macrophages within the population of CD45+ leukocytes is reduced by 11% in adult males (J:313172)

abnormal monocyte morphology ( J:60741 )

• on day 1 after treatment mutants have a lower percentage of monocytes/macrophages

decreased monocyte cell number ( J:60741 )

abnormal leukocyte physiology ( J:60741 )

• leukocytes from mutants show weaker NF-kappa b binding activity upon stimulation with thioglycollate broth than wild-type controls

abnormal macrophage physiology ( J:60741 )

• peritoneal macrophages show decreased areas of adherence in culture compared to wild-type

increased macrophage apoptosis ( J:60741 )

• Lgals-deficient macrophages are more sensitive to apoptotic stimuli in culture

digestive/alimentary system

peritoneal inflammation ( J:60741 )

• Lgals-deficient mice display attenuated peritoneal inflammation compared to wild-type upon stimulation with thioglycollate broth administration

cellular

decreased male germ cell number ( J:313172 )

♂ • testes show a significant reduction in male germ cell number at P5 and P15

♂ • reduced number of gonocytes and spermatogonia is independent of proliferation

increased macrophage apoptosis ( J:60741 )

• Lgals-deficient macrophages are more sensitive to apoptotic stimuli in culture

increased male germ cell apoptosis ( J:313172 )

♂ • at P5, P35, P50 and P100, testes exhibit a significantly higher number of TUNEL+ apoptotic germ cells than wild-type testes

♂ • at P50, testes show downregulated expression of the anti-apoptotic protein BCL2 but upregulated expression of the proapoptotic proteins BAK1 and BAX, indicating an imbalance in anti-/pro-apoptotic protein expression

reproductive system

decreased male germ cell number ( J:313172 )

♂ • testes show a significant reduction in male germ cell number at P5 and P15

♂ • reduced number of gonocytes and spermatogonia is independent of proliferation

increased male germ cell apoptosis ( J:313172 )

♂ • at P5, P35, P50 and P100, testes exhibit a significantly higher number of TUNEL+ apoptotic germ cells than wild-type testes

♂ • at P50, testes show downregulated expression of the anti-apoptotic protein BCL2 but upregulated expression of the proapoptotic proteins BAK1 and BAX, indicating an imbalance in anti-/pro-apoptotic protein expression

abnormal seminiferous tubule morphology ( J:313172 )

♂ • however, by P35, all seminiferous tubules contain germ cells

♂ • at P15, the % of tubules containing a lumen is 2-fold lower than in wild-type tubules

♂ • 8% of tubules at P15 and ~15% of tubules at P20 contain no germ cells

♂ • at P5, the number of seminiferous tubules without germ cells is significantly increased compared to wild-type testes (46% versus 13%, respectively)

abnormal Sertoli cell development ( J:313172 )

♂ • Sertoli cell maturation is delayed, as shown by 3-fold increase in the mRNA levels of anti-Mullerian hormone (Amh) at P15

♂ • however, at P15, the overall number of Sertoli cells is unaffected

decreased testis weight ( J:313172 )

♂ • at P50 and P100, testicular weight is significantly lower than in wild-type males

testicular atrophy ( J:313172 )

♂ • adult males exhibit mild testicular atrophy

abnormal testis physiology ( J:313172 )

♂ • gene and protein expression of Insl3 (insulin-like-3, a Leydig cell marker) and enzymes involved in steroid biosynthesis are significantly upregulated in adult testes

♂ • the % of testicular macrophages within the population of CD45+ leukocytes is reduced by 11% in adult males

abnormal spermatogenesis ( J:313172 )

♂ • males show a delay in the first wave of spermatogenesis

♂ • at P15, most of the differentiated germ cells consist of zygotene spermatocytes with numerous tubules containing only spermatogonia; the % of tubules containing pachytene spermatocytes is significantly lower than in wild-type testes (9% versus 23%, respectively)

♂ • at P20, most tubules contain only pachytene spermatocytes (a mid-meiotic stage); the % of tubules containing round spermatids and pachytene spermatocytes is significantly lower than in wild-type testes (3.6% versus 17% and 53% versus 82%, respectively)

♂ • by P20, the % of tubules containing less-differentiated cells such as leptotene/zygotene spermatocytes or spermatogonia) is significantly higher than in wild-type testes (14% versus 3.7% and 18% versus 0%, respectively)

homeostasis/metabolism

increased circulating testosterone level ( J:313172 )

♂ • at P50, serum testosterone levels are significantly higher than in wild-type males

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:313172 )

♂ • at P5, the number of seminiferous tubules without germ cells is significantly increased compared to wild-type testes (46% versus 13%, respectively)

♂ • at P15, the % of tubules containing a lumen is 2-fold lower than in wild-type tubules

♂ • 8% of tubules at P15 and ~15% of tubules at P20 contain no germ cells

♂ • however, by P35, all seminiferous tubules contain germ cells

abnormal Sertoli cell development ( J:313172 )

♂ • Sertoli cell maturation is delayed, as shown by 3-fold increase in the mRNA levels of anti-Mullerian hormone (Amh) at P15

♂ • however, at P15, the overall number of Sertoli cells is unaffected

decreased testis weight ( J:313172 )

♂ • at P50 and P100, testicular weight is significantly lower than in wild-type males

testicular atrophy ( J:313172 )

♂ • adult males exhibit mild testicular atrophy

abnormal testis physiology ( J:313172 )

♂ • gene and protein expression of Insl3 (insulin-like-3, a Leydig cell marker) and enzymes involved in steroid biosynthesis are significantly upregulated in adult testes

♂ • the % of testicular macrophages within the population of CD45+ leukocytes is reduced by 11% in adult males

Genotype
MGI:5637814

hm3

• Allelic Composition: Lgals3^tm1Ftl/Lgals3^tm1Ftl
• Genetic Background: involves: 129S2/SvPas * CD-1

liver/biliary system

liver inflammation ( J:221030 )

♂ • neutrophil aggregation in the liver lobules and lymphocyte-predominant lobular inflammation with or without portal inflammation are seen at varying degrees after 15 months of age

♂ • necroinflammation worsens with age focal hepatic necrosis

abnormal liver morphology ( J:116073 , J:221030 )

♂ • neutrophil infiltration, Mallory bodies, and megamitochondria are seen occasionally in 6 month old mice (J:116073)

♂ • 40%, 50%, and 100% of mice exhibit dysplastic liver nodules of various sizes at 15, 20, and 25 months of age, respectively (J:221030)

♂ • nodules have no capsule and exhibit increased cellularity with irregular hepatocellular arrangement and cellular atypia is frequently seen (J:221030)

increased liver weight ( J:116073 )

♂ • the liver weight per body weight ratio is increased at 6 months of age

increased liver triglyceride level ( J:116073 )

♂ • in 6 month old mice

abnormal hepatocyte morphology ( J:116073 )

♂ • hepatocytes of 6 month old mice show ballooning degeneration and scattered lipogranuloma

Mallory bodies ( J:116073 )

♂ • Mallory bodies are seen occasionally in 6 month old mice

focal hepatic necrosis ( J:116073 , J:221030 )

♂ • focal and/or spotty necrosis are seen occasionally in 6 month old mice (J:116073)

♂ (J:221030)

hepatic steatosis ( J:116073 , J:221030 )

♂ • livers show mild to severe macrovesicular and microvesicular fatty change which is enhanced in the perivenular area at 6 months of age (J:116073)

♂ • the macro- and micro-vacuoles of hepatocytes contain lipids at 6 months of age (J:116073)

♂ • mice develop features similar to nonalcoholic fatty liver disease that progresses to nonalcoholic steatohepatitis (J:221030)

♂ • the degree of steatosis decreases with age, fat vesicles accumulating in hepatocytes become smaller in size and the distribution diffused in the liver parenchyma (J:221030)

increased hepatocellular carcinoma incidence ( J:221030 )

♂ • inner nodules showing thick trabecular arrangement and pseudoglandular pattern are indicative of moderately differentiated hepatocellular carcinoma

liver fibrosis ( J:221030 )

♂ • 40%, 75%, and 100% of mice develop mild to moderate perivenular and pericellular fibrosis at 15, 20, and 25 months of age, respectively

homeostasis/metabolism

increased circulating alanine transaminase level ( J:116073 )

♂ • in 6 month old mice

increased liver triglyceride level ( J:116073 )

♂ • in 6 month old mice

cellular

oxidative stress ( J:116073 )

♂ • lipid peroxide levels are higher in the liver at 2 and 6 months of age, indicating oxidative stress

immune system

liver inflammation ( J:221030 )

♂ • neutrophil aggregation in the liver lobules and lymphocyte-predominant lobular inflammation with or without portal inflammation are seen at varying degrees after 15 months of age

♂ • necroinflammation worsens with age focal hepatic necrosis

neoplasm

increased hepatocellular carcinoma incidence ( J:221030 )

♂ • inner nodules showing thick trabecular arrangement and pseudoglandular pattern are indicative of moderately differentiated hepatocellular carcinoma

growth/size/body

increased liver weight ( J:116073 )

♂ • the liver weight per body weight ratio is increased at 6 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
steatotic liver disease		DOID:9452	OMIM:228100	J:116073 , J:221030

Genotype
MGI:3789178

cx4

• Allelic Composition: Cys1^cpk/Cys1^cpk; Lgals3^tm1Ftl/Lgals3^tm1Ftl
• Genetic Background: B6.Cg-Cys1^cpk Lgals3^tm1Ftl

renal/urinary system

kidney cyst ( J:116210 )

• mice develop medullary and cortical cysts

• however, gross ciliary structure is normal

kidney cortex cyst ( J:116210 )

• mice develop more cortical cysts than in Cys1^cpk homozygotes

growth/size/body

kidney cyst ( J:116210 )

• mice develop medullary and cortical cysts

• however, gross ciliary structure is normal

kidney cortex cyst ( J:116210 )

• mice develop more cortical cysts than in Cys1^cpk homozygotes

Genotype
MGI:3789176

cx5

• Allelic Composition: Cys1^cpk/Cys1^cpk; Lgals3^tm1Ftl/Lgals3^tm1Ftl
• Genetic Background: involves: 129/Sv * C57BL/6

renal/urinary system

kidney cyst ( J:116210 )

• mice develop medullary and cortical cysts

• however, gross ciliary structure is normal

kidney cortex cyst ( J:116210 )

• mice develop more cortical cysts than in Cys1^cpk homozygotes

increased kidney weight ( J:116210 )

• mice exhibit an increase in kidney weight and kidney weight to body weight ratio compared to in Lgals3^tm1Poi homozygotes

growth/size/body

kidney cyst ( J:116210 )

• mice develop medullary and cortical cysts

• however, gross ciliary structure is normal

kidney cortex cyst ( J:116210 )

• mice develop more cortical cysts than in Cys1^cpk homozygotes

increased kidney weight ( J:116210 )

• mice exhibit an increase in kidney weight and kidney weight to body weight ratio compared to in Lgals3^tm1Poi homozygotes