Phenotypes associated with this allele

• Allele Symbol: Fyn^tm1Sor
• Allele Name: targeted mutation 1, Philippe Soriano
• Allele ID: MGI:1857172
• Summary: 11 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fyn^tm1Sor/Fyn^tm1Sor	B6.129S7-Fyn^tm1Sor	MGI:3809403
hm2	Fyn^tm1Sor/Fyn^tm1Sor	either: 129S7/SvEvBrd-Fyn^tm1Sor or (involves: 129S7/SvEvBrd * C57BL/6J)	MGI:2175034
hm3	Fyn^tm1Sor/Fyn^tm1Sor	involves: 129S7/SvEvBrd	MGI:3815319
hm4	Fyn^tm1Sor/Fyn^tm1Sor	involves: 129S7/SvEvBrd * C57BL/6J	MGI:3640282
cn5	Fyn^tm1Sor/Fyn^tm1Sor Lck^tm1Litt/Lck^tm1.1Litt Tnfrsf4^tm2(cre)Nik/Tnfrsf4^+	involves: 129S7/SvEvBrd * 129X1/SvJ	MGI:4359000
cx6	Blk^tm1Tara/Blk^tm1Tara Fyn^tm1Sor/Fyn^tm1Sor Lyn^tm1Ard/Lyn^tm1Ard	either: B6.129-Lyn^tm1Ard Fyn^tm1Sor Blk^tm1Tara or (involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6)	MGI:3696475
cx7	Fyn^tm1Sor/Fyn^tm1Sor Src^tm1Sor/Src^+	involves: 129S7/SvEvBrd	MGI:3574822
cx8	Fyn^tm1Sor/Fyn^tm1Sor Yes1^tm1Sor/Yes1^tm1Sor	involves: 129S7/SvEvBrd	MGI:3574820
cx9	Fyn^tm1Sor/Fyn^tm1Sor Src^tm1Sor/Src^tm1Sor	involves: 129S7/SvEvBrd	MGI:3795906
cx10	Fyn^tm1Sor/Fyn^tm1Sor Tg(Camk2a-Fyn)1Kndl/0	involves: 129S7/SvEvBrd * C57BL/6 * CBA	MGI:3693372
cx11	Fyn^tm1Sor/Fyn^+ Tg(Camk2a-Fyn-531)1Nko/0	involves: 129S7/SvEvBrd * C57BL/6 * CBA	MGI:2652121

Genotype
MGI:3809403

hm1

• Allelic Composition: Fyn^tm1Sor/Fyn^tm1Sor
• Genetic Background: B6.129S7-Fyn^tm1Sor

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

immune system

abnormal T cell proliferation ( J:93886 )

decreased IgE level ( J:93886 )

• levels are dramatically reduced

abnormal NK cell physiology ( J:187430 )

• decreased killing of RMA-S, B16 and, to a lesser extent, YAC-1 cells

• reduced activating effect of 2B4 towards cytotoxicity

• reduced conjugation with RMA-S cells, less pronounced than in Sh2d1a^tm1Pls homozygotes

abnormal CD4-positive, alpha-beta T cell physiology ( J:93886 )

• pronounced defects in TCR-initiated proliferation and production of Ifng, IL-4 and IL-2 upon stimulation with anti-CD3 or anti-CD3 plus anti-CD28

• some responses are partially corrected by addition of exogenous IL-2, but IL-4 production block is not relieved

• cells exhibit impaired IL-4 and IL-13 production upon stimulation with anti-CD3, anti-CD3 and anti-CD28 or PMA plus ionomycin

decreased interferon-gamma secretion ( J:187430 )

• in response to RMA-S

hematopoietic system

abnormal T cell proliferation ( J:93886 )

decreased IgE level ( J:93886 )

• levels are dramatically reduced

abnormal NK cell physiology ( J:187430 )

• decreased killing of RMA-S, B16 and, to a lesser extent, YAC-1 cells

• reduced activating effect of 2B4 towards cytotoxicity

• reduced conjugation with RMA-S cells, less pronounced than in Sh2d1a^tm1Pls homozygotes

abnormal CD4-positive, alpha-beta T cell physiology ( J:93886 )

• pronounced defects in TCR-initiated proliferation and production of Ifng, IL-4 and IL-2 upon stimulation with anti-CD3 or anti-CD3 plus anti-CD28

• some responses are partially corrected by addition of exogenous IL-2, but IL-4 production block is not relieved

• cells exhibit impaired IL-4 and IL-13 production upon stimulation with anti-CD3, anti-CD3 and anti-CD28 or PMA plus ionomycin

cellular

abnormal T cell proliferation ( J:93886 )

Genotype
MGI:2175034

hm2

• Allelic Composition: Fyn^tm1Sor/Fyn^tm1Sor
• Genetic Background: either: 129S7/SvEvBrd-Fyn^tm1Sor or (involves: 129S7/SvEvBrd * C57BL/6J)

immune system

abnormal T cell clonal deletion ( J:2242 )

• thymocytes are impaired in a late stage of maturation and show limited clonal deletion to the Mls-1a self-superantigen but not to staphylococcal enterotoxin A

abnormal immune cell physiology ( J:2242 )

• thymocytes and mature T cells fail to flux calcium to any large extent in response to TCR cross-linking

increased IgG2a level ( J:2242 )

• IgG2a is consistently elevated by 30-40%

increased IgM level ( J:2242 )

• consistently elevated by 30-40%

abnormal T cell physiology ( J:2242 )

• mature T cells fail to flux calcium to any large extent in response to TCR cross-linking

decreased T cell proliferation ( J:2242 )

• thymocytes of each single positive phenotype fail to proliferate in response to anti-CD3 and PMA, in contrast with single positive wild-type thymocytes

abnormal thymocyte activation ( J:2242 )

• proliferation of thymocytes in response to anti-CD3 or anti-Thy-1 cross-linking is substantially compromised, however peripheral T cell activation responses are largely functional

decreased interleukin-2 secretion ( J:2242 )

• production of IL-2 by splenic T cells is reduced in response to TCR activation

behavior/neurological

abnormal spatial learning ( J:3417 )

• show impaired spatial learning in Morris water maze test

nervous system

abnormal dentate gyrus morphology ( J:3417 )

• exhibit an increased number of granule cells in the dentate gyrus

• exhibit undulation of the granule cell layer

abnormal hippocampus pyramidal cell layer ( J:3417 )

• undulation of the pyramidal cell layer in the CA3 region and in the dentate gyrus

abnormal hippocampus pyramidal cell morphology ( J:3417 )

• apical dendrites of CA1 pyramidal neurons appear less tightly organized

increased hippocampus pyramidal cell number ( J:3417 )

• exhibit an increased number of pyramidal cells in the CA3 region

reduced long-term potentiation ( J:3417 )

• LTP is blunted in the CA1 neurons of hippocampal slices, in both the field EPSP and in the population spike, even though synaptic transmission and two short-term forms of synaptic plasticity, paired-pulse facilitation and post-tetanic

hematopoietic system

abnormal T cell clonal deletion ( J:2242 )

• thymocytes are impaired in a late stage of maturation and show limited clonal deletion to the Mls-1a self-superantigen but not to staphylococcal enterotoxin A

increased IgG2a level ( J:2242 )

• IgG2a is consistently elevated by 30-40%

increased IgM level ( J:2242 )

• consistently elevated by 30-40%

abnormal T cell physiology ( J:2242 )

• mature T cells fail to flux calcium to any large extent in response to TCR cross-linking

decreased T cell proliferation ( J:2242 )

• thymocytes of each single positive phenotype fail to proliferate in response to anti-CD3 and PMA, in contrast with single positive wild-type thymocytes

abnormal thymocyte activation ( J:2242 )

• proliferation of thymocytes in response to anti-CD3 or anti-Thy-1 cross-linking is substantially compromised, however peripheral T cell activation responses are largely functional

endocrine/exocrine glands

abnormal thymocyte activation ( J:2242 )

• proliferation of thymocytes in response to anti-CD3 or anti-Thy-1 cross-linking is substantially compromised, however peripheral T cell activation responses are largely functional

cellular

decreased T cell proliferation ( J:2242 )

• thymocytes of each single positive phenotype fail to proliferate in response to anti-CD3 and PMA, in contrast with single positive wild-type thymocytes

Genotype
MGI:3815319

hm3

• Allelic Composition: Fyn^tm1Sor/Fyn^tm1Sor
• Genetic Background: involves: 129S7/SvEvBrd

immune system

abnormal macrophage physiology ( J:80658 )

• fibrillar beta-amyloid stimulated reactive oxygen species production is reduced 90% compared to in wild-type cells

• however, response to zymosan is normal

abnormal chemokine level ( J:80658 )

• fibrillar beta-amyloid stimulated MCP-1 production in macrophages is reduced to 75% of wild-type

homeostasis/metabolism

abnormal chemokine level ( J:80658 )

• fibrillar beta-amyloid stimulated MCP-1 production in macrophages is reduced to 75% of wild-type

hematopoietic system

abnormal macrophage physiology ( J:80658 )

• fibrillar beta-amyloid stimulated reactive oxygen species production is reduced 90% compared to in wild-type cells

• however, response to zymosan is normal

Genotype
MGI:3640282

hm4

• Allelic Composition: Fyn^tm1Sor/Fyn^tm1Sor
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

nervous system

decreased corpus callosum size ( J:109485 )

• thickness of corpus callosum is reduced compared to wild-type

abnormal hippocampus morphology ( J:80637 )

abnormal dentate gyrus morphology ( J:80637 )

• abnormal arrangement of rostral dentate gyrus

abnormal hippocampus pyramidal cell layer ( J:80637 )

• CA1 pyramidal cells are less tightly packed

• caudal CA3 pyramidal cell regions shows an abnormal arrangement

abnormal hippocampus pyramidal cell morphology ( J:80637 )

• dendritic regions of pyramidal cells are narrow and length of the apical dendrites is shortened

ectopic hippocampus pyramidal cells ( J:80637 )

• ectopic pyramidal cells are frequently seen

abnormal optic nerve morphology ( J:109485 )

• there is a 15% reduction in cross-sectional area of the optic nerve compared to wild-type

abnormal myelination ( J:109485 )

• in the forebrain from P14 to P385, a myelin deficit is observed; at P26, deficit is 52% compared to controls

• myelin basic protein content in the brain is significantly reduced with a magnitude of 40%

reduced long-term potentiation ( J:80637 )

• exhibit age-dependent impairment of LTP that appears only when homozygotes are over 10 weeks of age

vision/eye

abnormal optic nerve morphology ( J:109485 )

• there is a 15% reduction in cross-sectional area of the optic nerve compared to wild-type

reproductive system

reproductive system phenotype ( J:185783 )

♂N • despite their reduced epididymal size and sperm count, male mice produce normal litter sizes when mated with wild-type females and are technically fertile

abnormal sperm motility ( J:185783 )

♂ • in vitro, cauda epididymal sperm show small but significant reductions in total, progressive, and hyperactive motility and increased local (twitching, nonprogressive) motility before capacitation

♂ • after capacitation, sperm show normal total and hyperactive motility, a slight increase in progressive motility, and a small reduction in local motility, suggesting that differences in motility parameters are relatively minor

abnormal spermatogenesis ( J:185783 )

♂ • later stages of spermatogenesis are negatively impacted

oligozoospermia ( J:185783 )

♂ • at 7-8 weeks of age, epididymal sperm count is significantly lower than that in wild-type males

teratozoospermia ( J:185783 )

♂ • males show a high frequency of morphological defects in cauda epididymal sperm

abnormal sperm connecting piece morphology ( J:185783 )

♂ • incorrect head-to-neck connections are commonly observed

abnormal sperm head morphology ( J:185783 )

♂ • club-shaped and triangular head morphologies and incorrect head-to-neck connections are commonly observed

abnormal spermiogenesis ( J:185783 )

♂ • abnormal sperm head structures are observed during spermiogenesis

abnormal sperm capacitation ( J:185783 )

♂ • in vitro capacitated sperm show slight alterations in the pattern of capacitation-induced protein tyrosine phosphorylation, with decreased abundance of several minor phosphoproteins

decreased epididymis weight ( J:185783 )

♂ • at 7-8 weeks of age, epididymal weight is significantly lower than that in wild-type males

♂ • however, testis weight is normal

impaired acrosome reaction ( J:185783 )

♂ • following in vitro capacitation, the rate of A23187-induced acrosome reaction in cauda epididymal sperm is significantly lower than that in wild-type sperm

♂ • however, in the absence of induction, sperm show the same low frequency of spontaneous acrosome reactions as wild-type sperm

decreased fertilization frequency ( J:185783 )

♂ • an in vivo competitive artificial insemination trial showed that the average % of embryos produced per female by mutant epididymal sperm is about one-sixth of that produced by wild-type sperm (14.4% versus 85.6%), indicating impaired sperm fertilizing capacity

impaired sperm penetration of zona pellucida ( J:185783 )

♂ • in an IVF assay, sperm show a significantly reduced ability to penetrate the zona pellucida than wild-type sperm, resulting in a lower frequency of sperm retained in the perivitelline space or fused with the ooplasm

cellular

oligozoospermia ( J:185783 )

♂ • at 7-8 weeks of age, epididymal sperm count is significantly lower than that in wild-type males

teratozoospermia ( J:185783 )

♂ • males show a high frequency of morphological defects in cauda epididymal sperm

abnormal sperm connecting piece morphology ( J:185783 )

♂ • incorrect head-to-neck connections are commonly observed

abnormal sperm head morphology ( J:185783 )

♂ • club-shaped and triangular head morphologies and incorrect head-to-neck connections are commonly observed

abnormal sperm motility ( J:185783 )

♂ • in vitro, cauda epididymal sperm show small but significant reductions in total, progressive, and hyperactive motility and increased local (twitching, nonprogressive) motility before capacitation

♂ • after capacitation, sperm show normal total and hyperactive motility, a slight increase in progressive motility, and a small reduction in local motility, suggesting that differences in motility parameters are relatively minor

Genotype
MGI:4359000

cn5

• Allelic Composition: Fyn^tm1Sor/Fyn^tm1Sor; Lck^tm1Litt/Lck^tm1.1Litt; Tnfrsf4^tm2(cre)Nik/Tnfrsf4⁺
• Genetic Background: involves: 129S7/SvEvBrd * 129X1/SvJ

immune system

decreased T cell proliferation ( J:152472 )

• CD25+ T cells fail to proliferate when transferred into T cell-deficient recipients unlike similarly treated wild-type cells

• CD25- T cells exhibit reduced proliferation when transferred into T cell deficient recipients compared with similarly treated wild-type cells

decreased regulatory T cell number ( J:152472 )

• in the thymus and spleen

increased T cell number ( J:152472 )

increased regulatory T cell number ( J:152472 )

• in the lymph node

abnormal regulatory T cell physiology ( J:152472 )

• regulatory T cell turnover is impaired and suppressive function is lost

enlarged lymph nodes ( J:152472 )

• mild

hematopoietic system

decreased T cell proliferation ( J:152472 )

• CD25+ T cells fail to proliferate when transferred into T cell-deficient recipients unlike similarly treated wild-type cells

• CD25- T cells exhibit reduced proliferation when transferred into T cell deficient recipients compared with similarly treated wild-type cells

decreased regulatory T cell number ( J:152472 )

• in the thymus and spleen

increased T cell number ( J:152472 )

increased regulatory T cell number ( J:152472 )

• in the lymph node

abnormal regulatory T cell physiology ( J:152472 )

• regulatory T cell turnover is impaired and suppressive function is lost

cellular

decreased T cell proliferation ( J:152472 )

• CD25+ T cells fail to proliferate when transferred into T cell-deficient recipients unlike similarly treated wild-type cells

• CD25- T cells exhibit reduced proliferation when transferred into T cell deficient recipients compared with similarly treated wild-type cells

Genotype
MGI:3696475

cx6

• Allelic Composition: Blk^tm1Tara/Blk^tm1Tara; Fyn^tm1Sor/Fyn^tm1Sor; Lyn^tm1Ard/Lyn^tm1Ard
• Genetic Background: either: B6.129-Lyn^tm1Ard Fyn^tm1Sor Blk^tm1Tara or (involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6)

immune system

abnormal B cell differentiation ( J:115080 )

• mutant bone marrow is unable to reconstitute B cell development when transferred into lethally irradiated C57BL/6 mice

decreased immature B cell number ( J:115080 )

• exhibit a decrease in immature and B cells in the bone marrow

abnormal pro-B cell differentiation ( J:115080 )

• pro-B cells exhibit impaired anti-Igbeta-induced NF-kappaB activation

arrested B cell differentiation ( J:115080 )

• block in early B cell development

decreased B cell number ( J:115080 )

• impaired development of B cells results in severe B cell lymphopenia characterized by a decrease in B cell numbers in the spleen, lymph nodes, and peritoneal cavity to 1/60-1/100 of wild-type

decreased pre-B cell number ( J:115080 )

• exhibit a reduction in the fraction of viable B220+CD43-IgM- pre-B cells to 10% of wild-type

• 3-fold increase in frequency of apoptotic pre-B cells

hematopoietic system

abnormal B cell differentiation ( J:115080 )

• mutant bone marrow is unable to reconstitute B cell development when transferred into lethally irradiated C57BL/6 mice

decreased immature B cell number ( J:115080 )

• exhibit a decrease in immature and B cells in the bone marrow

abnormal pro-B cell differentiation ( J:115080 )

• pro-B cells exhibit impaired anti-Igbeta-induced NF-kappaB activation

arrested B cell differentiation ( J:115080 )

• block in early B cell development

decreased B cell number ( J:115080 )

• impaired development of B cells results in severe B cell lymphopenia characterized by a decrease in B cell numbers in the spleen, lymph nodes, and peritoneal cavity to 1/60-1/100 of wild-type

decreased pre-B cell number ( J:115080 )

• exhibit a reduction in the fraction of viable B220+CD43-IgM- pre-B cells to 10% of wild-type

• 3-fold increase in frequency of apoptotic pre-B cells

Genotype
MGI:3574822

cx7

• Allelic Composition: Fyn^tm1Sor/Fyn^tm1Sor; Src^tm1Sor/Src⁺
• Genetic Background: involves: 129S7/SvEvBrd

behavior/neurological

abnormal nursing ( J:20346 )

♀ • difficulty in nursing newborn pups on the occasional cases where females became pregnant

reproductive system

reduced female fertility ( J:20346 )

♀

Genotype
MGI:3574820

cx8

• Allelic Composition: Fyn^tm1Sor/Fyn^tm1Sor; Yes1^tm1Sor/Yes1^tm1Sor
• Genetic Background: involves: 129S7/SvEvBrd

mortality/aging

postnatal lethality, incomplete penetrance ( J:20346 )

• incomplete penetrance; only 35% of animals survived to weaning age; normal Mendelian ratios were present at E18.5

growth/size/body

decreased body size ( J:20346 )

• animals were described as smaller at weaning age

weight loss ( J:20346 )

• at 3-5 months of age, surviving animals began to lose weight

enlarged spleen ( J:20346 )

• due to prominent myeloid hyperplasia and expansion of the white pulp

hematopoietic system

enlarged spleen ( J:20346 )

• due to prominent myeloid hyperplasia and expansion of the white pulp

myeloid hyperplasia ( J:20346 )

extramedullary hematopoiesis ( J:20346 )

increased spleen white pulp amount ( J:20346 )

• expansion of the white pulp

homeostasis/metabolism

increased urine protein level ( J:20346 )

• greater than 100mg/dl with presence of leukocytes and erythrocytes in the urine

immune system

enlarged spleen ( J:20346 )

• due to prominent myeloid hyperplasia and expansion of the white pulp

myeloid hyperplasia ( J:20346 )

increased spleen white pulp amount ( J:20346 )

• expansion of the white pulp

renal/urinary system

increased urine protein level ( J:20346 )

• greater than 100mg/dl with presence of leukocytes and erythrocytes in the urine

abnormal kidney morphology ( J:20346 )

• pale with pitted surface

abnormal renal glomerulus morphology ( J:20346 )

• expanded mesangial matrix with paramesangial deposits

• diffuse mesangial hypercellularity in focal glomeruli

cortical renal glomerulopathies ( J:20346 )

• evident at 5 weeks of age

glomerulosclerosis ( J:20346 )

• segmental glomerulosclerosis

small kidney ( J:20346 )

• described as shrunken

abnormal renal tubule morphology ( J:20346 )

• renal interstitium displayed tubal ectasia and chronic inflammatory cell infiltrate with IgG, IgM, IgA and complement C3 deposits in the mesangium, but no evidence of autoimmune disease was observed

nervous system

abnormal hippocampus morphology ( J:20346 )

• undulations of the CA3 region; no more severe than in homozygous Fyn mutant mice

abnormal dentate gyrus morphology ( J:20346 )

• undulations; no more severe than in homozygous Fyn mutant mice

integument

ruffled hair ( J:20346 )

• observed at 3-5 months of age

Genotype
MGI:3795906

cx9

• Allelic Composition: Fyn^tm1Sor/Fyn^tm1Sor; Src^tm1Sor/Src^tm1Sor
• Genetic Background: involves: 129S7/SvEvBrd

mortality/aging

postnatal lethality, complete penetrance ( J:20346 )

• only 10% of animals survived to weaning age; normal Mendelian ratios were present at E18.5; animals did not survive past 3 weeks of age

growth/size/body

decreased body size ( J:20346 )

• animals were described as very small

decreased body weight ( J:20346 )

• at 3 weeks of age, animals weighed 3-4 grams compared to controls weighing 8 grams

Genotype
MGI:3693372

cx10

• Allelic Composition: Fyn^tm1Sor/Fyn^tm1Sor; Tg(Camk2a-Fyn)1Kndl/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CBA

nervous system

abnormal hippocampus morphology ( J:80637 )

• do not exhibit rescue of the morphological defects of the hippocampus that are seen in single Fyn homozygotes, however Schaffer collateral LTP is restored

abnormal dentate gyrus morphology ( J:80637 )

• dorsal part of the dentate gyrus granular cell layer is occasionally perturbed

abnormal hippocampus pyramidal cell layer ( J:80637 )

• caudal part of CA3 pyramidal cell layer is undulated and CA1 pyramidal cells are less tightly packed

abnormal hippocampus pyramidal cell morphology ( J:80637 )

• dendritic regions of pyramidal cells are narrow and length of the apical dendrites is shortened

ectopic hippocampus pyramidal cells ( J:80637 )

• ectopic pyramidal cells are frequently seen

Genotype
MGI:2652121

cx11

• Allelic Composition: Fyn^tm1Sor/Fyn⁺; Tg(Camk2a-Fyn-531)1Nko/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CBA

mortality/aging

premature death ( J:59490 )

• sudden death after weaning; survival rate shows correlation with level of transgene expression

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:59490 )

• lines expressing high levels of the transgene show spontaneous running and bouncing fits

tonic seizures ( J:59490 )

• tonic convulsion

nervous system

tonic seizures ( J:59490 )

• tonic convulsion