Phenotypes associated with this allele

• Allele Symbol: Sptlc2^tm1Yhir
• Allele Name: targeted mutation 1, Yoshio Hirabayashi
• Allele ID: MGI:5523495
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Sptlc2^tm1Yhir/Sptlc2^tm1Yhir Tg(KRT5-cre)1Tak/0	involves: C3H * C57BL/6	MGI:5563659
cn2	Sptlc2^tm1Yhir/Sptlc2^tm1Yhir Gt(ROSA)26Sor^tm9(cre/ESR1)Arte/Gt(ROSA)26Sor^+	involves: C57BL/6 * C57BL/6NTac	MGI:5523516

Genotype
MGI:5563659

cn1

• Allelic Composition: Sptlc2^tm1Yhir/Sptlc2^tm1Yhir; Tg(KRT5-cre)1Tak/0
• Genetic Background: involves: C3H * C57BL/6

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

mortality/aging

premature death ( J:202388 )

• most mice die by P25

growth/size/body

postnatal growth retardation ( J:202388 )

• mice show growth retardation after P7

integument

abnormal dendritic epidermal T cell morphology ( J:202388 )

• dendritic epidermal T cells in the epidermis undergo morphological alterations such as spherical change and loss of dendrites

impaired skin barrier function ( J:202388 )

• skin barrier function becomes disrupted and worsens from 2 weeks of age onward

skin inflammation ( J:202388 )

• cell infiltrates in the dermis

• neutrophil infiltrates in the upper dermis and sub-to-intracorneal neutrophil accumulation resembling the Munro's micro-abscess

• treatment with an anti-IL-12/23p40 antibody greatly attenuates the skin inflammation and epidermal hyperplasia and decreases the number of gamma-delta-17 cells in skin-draining lymph nodes

alopecia ( J:202388 )

• develop alopecia in the periocular and upper back areas and are covered with thick scales

sparse hair ( J:202388 )

• sparse hair after P7

abnormal epidermis stratum corneum morphology ( J:202388 )

• lipid inclusions in the stratum corneum

hyperkeratosis ( J:202388 )

• seen from 3 weeks of age

• hyperkeratosis is also seen in epithelia of the esophagus and the forestomach

abnormal epidermis stratum granulosum morphology ( J:202388 )

• vesicles in the stratum granulosum layer

abnormal epidermal lamellar body morphology ( J:202388 )

• abnormal lamellar bodies and malformation of lamellar structures

• lamellar bodies in P14, but not in newborns, have abnormal globular inclusions

• numbers of lamellar bodies within keratinocytes in the granular layer decline from 2 weeks onward

• delay in lamellar body secretion into the extracellular space after tape stripping

absent epidermis stratum granulosum ( J:202388 )

• loss of the granular layer

acanthosis ( J:202388 )

• acanthosis seen in mice older than 2 weeks of age

epidermal hyperplasia ( J:202388 )

dry skin ( J:202388 )

• newborns show generalized xerosis

reddish skin ( J:202388 )

• generalized erythema is seen from 3 weeks of age

scaly skin ( J:202388 )

• scales over the body are seen after P7

skin lesions ( J:202388 )

• from 3 weeks of age, lesions deteriorate with alopecia, hyperkeratosis, and generalized erythema

• skin lesions show an accumulation of IL-23+CD11c+ cells in the dermis

psoriasis ( J:202388 )

delayed skin barrier formation ( J:202388 )

• mice at P3 show an elevation of transepidermal water loss at 2.5 hours after tape stripping, indicating a delay in barrier restoration

• delay in lamellar body secretion into the extracellular space after tape stripping

immune system

increased dendritic cell number ( J:202388 )

• numbers of migrating dendritic cells including langerin+ cells are increased in skin-draining lymph nodes at P11, however the increase in IL-17 gamma-delta T cells is not seen at this time yet

increased T-helper 17 cell number ( J:202388 )

• increase in IL-17 producing CD4+ cells (Th17) in skin-draining lymph nodes

increased gamma-delta T cell number ( J:202388 )

• increase in CD4-CD8- gamma-delta T cells and IL-22-producing gamma-delta T cells in skin-draining lymph nodes

• expansion of IL-17 producing gamma-delta T cells in skin lesions

• treatment with an anti-IL-12/23p40 antibody decreases the number of gamma-delta-17 cells in skin-draining lymph nodes

abnormal Langerhans cell morphology ( J:202388 )

• Langerhans cells appear to be spherical with fewer dendrites compared to wild-type mice

• Langerhans cells have elongated dendrites upward beneath the stratum corneum, indicating that Langerhans cells are activated unlike wild-type Langerhans cells, which reside in the basal layer of the epidermis with horizontally spreading dendrites

abnormal dendritic epidermal T cell morphology ( J:202388 )

• dendritic epidermal T cells in the epidermis undergo morphological alterations such as spherical change and loss of dendrites

abnormal Langerhans cell physiology ( J:202388 )

• skin-draining lymph nodes exhibit increased numbers of CD40^highCD11c^int cells and of langerin+ cells, indicating enhanced Langerhans cell migration from the epidermis to lymph nodes

skin inflammation ( J:202388 )

• cell infiltrates in the dermis

• neutrophil infiltrates in the upper dermis and sub-to-intracorneal neutrophil accumulation resembling the Munro's micro-abscess

• treatment with an anti-IL-12/23p40 antibody greatly attenuates the skin inflammation and epidermal hyperplasia and decreases the number of gamma-delta-17 cells in skin-draining lymph nodes

hematopoietic system

increased dendritic cell number ( J:202388 )

• numbers of migrating dendritic cells including langerin+ cells are increased in skin-draining lymph nodes at P11, however the increase in IL-17 gamma-delta T cells is not seen at this time yet

increased T-helper 17 cell number ( J:202388 )

• increase in IL-17 producing CD4+ cells (Th17) in skin-draining lymph nodes

increased gamma-delta T cell number ( J:202388 )

• increase in CD4-CD8- gamma-delta T cells and IL-22-producing gamma-delta T cells in skin-draining lymph nodes

• expansion of IL-17 producing gamma-delta T cells in skin lesions

• treatment with an anti-IL-12/23p40 antibody decreases the number of gamma-delta-17 cells in skin-draining lymph nodes

abnormal Langerhans cell morphology ( J:202388 )

• Langerhans cells appear to be spherical with fewer dendrites compared to wild-type mice

• Langerhans cells have elongated dendrites upward beneath the stratum corneum, indicating that Langerhans cells are activated unlike wild-type Langerhans cells, which reside in the basal layer of the epidermis with horizontally spreading dendrites

abnormal dendritic epidermal T cell morphology ( J:202388 )

• dendritic epidermal T cells in the epidermis undergo morphological alterations such as spherical change and loss of dendrites

homeostasis/metabolism

dehydration ( J:202388 )

• water-holding capacity is reduced to 35% of the level in wild-type mice indicating constitutional impairment of hydration

impaired skin barrier function ( J:202388 )

• skin barrier function becomes disrupted and worsens from 2 weeks of age onward

abnormal ceramide level ( J:202388 )

• reduction of ceramide (Cer, d18:1/C18:0) in the epidermis of footpad skin

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
psoriasis		DOID:8893	OMIM:PS177900	J:202388

Genotype
MGI:5523516

cn2

• Allelic Composition: Sptlc2^tm1Yhir/Sptlc2^tm1Yhir; Gt(ROSA)26Sor^{tm9(cre/ESR1)Arte}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: C57BL/6 * C57BL/6NTac

hematopoietic system

abnormal thymus morphology ( J:202954 )

• 48 hours after tamoxifen treatment, mice exhibit slight lymphoid necrosis in the cortex of the thymus compared with control mice

• 72 hours after tamoxifen treatment, mice exhibit lymphoid necrosis in the thymus, predominantly in the periarterial lymphoid sheaths, with lymphoid depletion compared with control mice

decreased thymus weight ( J:202954 )

• 48 and 72 hours after tamoxifen treatment

decreased bone marrow cell number ( J:202954 )

• slight in tamoxifen treated mice at 48 hours of both erythroid and myeloid cells

• further decrease after 72 hours in tamoxifen-treated mice

increased erythrocyte cell number ( J:202954 )

• 72 hours after tamoxifen treatment

increased hematocrit ( J:202954 )

• 72 hours after tamoxifen treatment

increased hemoglobin content ( J:202954 )

• 72 hours after tamoxifen treatment

increased neutrophil cell number ( J:202954 )

• 72 hours after tamoxifen treatment

decreased lymphocyte cell number ( J:202954 )

• 48 and 72, but not 24, hours after tamoxifen treatment

reticulocytopenia ( J:202954 )

• 48 and 72, but not 24, hours after tamoxifen treatment

abnormal spleen morphology ( J:202954 )

• 72 hours after tamoxifen treatment, mice exhibit lymphoid necrosis in the spleen, predominantly in the periarterial lymphoid sheaths, with lymphoid depletion compared with control mice

decreased spleen weight ( J:202954 )

• 72 hours after tamoxifen treatment

digestive/alimentary system

abnormal pancreatic acinar cell zymogen granule morphology ( J:202954 )

• decreased at 72 hours in tamoxifen-treated mice

abnormal intestinal mucosa morphology ( J:202954 )

• 72 hours after tamoxifen treatment, mice exhibit atrophy of the small and large intestine mucosa with sloughing of mucosal epithelial cells and/or necrotic decries in the crypts compared with control mice

abnormal large intestine crypts of Lieberkuhn morphology ( J:202954 )

• 24 and 48 hours after tamoxifen treatment, mice exhibit several single cell necroses in the epithelia of small and large intestine crypts unlike control mice

abnormal small intestine crypts of Lieberkuhn morphology ( J:202954 )

• 24 and 48 hours after tamoxifen treatment, mice exhibit several single cell necroses in the epithelia of small and large intestine crypts unlike control mice

abnormal small intestinal villus morphology ( J:202954 )

• 48 hours after tamoxifen treatment, mice exhibit increased single cell necroses at the base of villi in the small intestine compared with control mice

abnormal stomach mucosa morphology ( J:202954 )

• 72 hours after tamoxifen treatment, mice exhibit atrophy of the stomach mucosa predominantly in the pyloric region and characterized by exfoliation of necrotic epithelial cells into the gastric lumen and thinning of the gastric epithelial cells, especially the gastric gland epithelium, compared with control mice

homeostasis/metabolism

increased blood urea nitrogen level ( J:202954 )

• in tamoxifen-treated mice

abnormal circulating protein level ( J:202954 )

• increased total protein in tamoxifen-treated mice

increased circulating alanine transaminase level ( J:202954 )

• in tamoxifen-treated mice

increased circulating serum albumin level ( J:202954 )

• total and albumin to globulin ratio in tamoxifen-treated mice

cellular

cellular necrosis ( J:202954 )

• 24 and 48 hours after tamoxifen treatment, mice exhibit several single cell necroses in the epithelia of small and large intestine crypts unlike control mice

• 48 hours after tamoxifen treatment, mice exhibit increased single cell necroses at the base of villi in the small intestine compared with control mice

• 48 hours after tamoxifen treatment, mice exhibit slight lymphoid necrosis in the cortex of the thymus compared with wild-type mice

• 72 hours after tamoxifen treatment, mice exhibit lymphoid necrosis in the thymus and spleen, predominantly in the periarterial lymphoid sheaths, with lymphoid depletion compared with control mice

integument

sebaceous gland atrophy ( J:202954 )

• slight at 72 hours in tamoxifen-treated mice

endocrine/exocrine glands

abnormal pancreatic acinar cell zymogen granule morphology ( J:202954 )

• decreased at 72 hours in tamoxifen-treated mice

abnormal large intestine crypts of Lieberkuhn morphology ( J:202954 )

• 24 and 48 hours after tamoxifen treatment, mice exhibit several single cell necroses in the epithelia of small and large intestine crypts unlike control mice

abnormal small intestine crypts of Lieberkuhn morphology ( J:202954 )

• 24 and 48 hours after tamoxifen treatment, mice exhibit several single cell necroses in the epithelia of small and large intestine crypts unlike control mice

increased adrenal gland weight ( J:202954 )

• increased adrenal gland weight at 72 hours after tamoxifen treatment

abnormal thymus morphology ( J:202954 )

• 48 hours after tamoxifen treatment, mice exhibit slight lymphoid necrosis in the cortex of the thymus compared with control mice

• 72 hours after tamoxifen treatment, mice exhibit lymphoid necrosis in the thymus, predominantly in the periarterial lymphoid sheaths, with lymphoid depletion compared with control mice

decreased thymus weight ( J:202954 )

• 48 and 72 hours after tamoxifen treatment

sebaceous gland atrophy ( J:202954 )

• slight at 72 hours in tamoxifen-treated mice

immune system

abnormal thymus morphology ( J:202954 )

• 48 hours after tamoxifen treatment, mice exhibit slight lymphoid necrosis in the cortex of the thymus compared with control mice

• 72 hours after tamoxifen treatment, mice exhibit lymphoid necrosis in the thymus, predominantly in the periarterial lymphoid sheaths, with lymphoid depletion compared with control mice

decreased thymus weight ( J:202954 )

• 48 and 72 hours after tamoxifen treatment

increased neutrophil cell number ( J:202954 )

• 72 hours after tamoxifen treatment

decreased lymphocyte cell number ( J:202954 )

• 48 and 72, but not 24, hours after tamoxifen treatment

abnormal spleen morphology ( J:202954 )

• 72 hours after tamoxifen treatment, mice exhibit lymphoid necrosis in the spleen, predominantly in the periarterial lymphoid sheaths, with lymphoid depletion compared with control mice

decreased spleen weight ( J:202954 )

• 72 hours after tamoxifen treatment