Phenotypes associated with this allele

• Allele Symbol: Pikfyve^tm2.1Tssk
• Allele Name: targeted mutation 2.1, Takehiko Sasaki
• Allele ID: MGI:5474981
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Pikfyve^tm2.1Tssk/Pikfyve^tm2.1Tssk Tg(Vil1-cre)20Syr/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:5474983
cn2	Pikfyve^tm2.1Tssk/Pikfyve^tm2.1Tssk Tg(Tyr-cre/ERT2)13Bos/0	involves: C57BL/6 * C57BL/6J	MGI:6256964
cn3	Gt(ROSA)26Sor^tm4(ACTB-tdTomato,-EGFP)Luo/Gt(ROSA)26Sor^+ Pikfyve^tm2.1Tssk/Pikfyve^tm2.1Tssk Tg(Tyr-cre/ERT2)13Bos/0	involves: C57BL/6 * C57BL/6J	MGI:6256968

Genotype
MGI:5474983

cn1

• Allelic Composition: Pikfyve^tm2.1Tssk/Pikfyve^tm2.1Tssk; Tg(Vil1-cre)20Syr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

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

mortality/aging

lethality, incomplete penetrance ( J:193689 )

• only 20% of mice born alive survive beyond 100 days

premature death ( J:193689 )

• only 20% of mice born alive survive beyond 100 days

prenatal lethality, incomplete penetrance ( J:193689 )

• recovered at a lower than expected Mendelian frequency

digestive/alimentary system

diarrhea ( J:193689 )

melena ( J:193689 )

abnormal enterocyte morphology ( J:193689 )

• enterocytes expressing cre have enlarged endosomes

• marked vacuolation of enterocytes in the ileum

• decrease in actin at the apical surface and ectopic localization of DPP4 and IAP

abnormal small intestinal microvillus morphology ( J:193689 )

• sparse in number

decreased small intestinal microvillus size ( J:193689 )

• short

intestinal fibrosis ( J:193689 )

• overt fibrosis of the muscularis mucosa

intestinal inflammation ( J:193689 )

• lymphocyte infiltration is prominent in both the mucosa and submucosa

homeostasis/metabolism

decreased circulating free fatty acids level ( J:193689 )

abnormal circulating enzyme level ( J:193689 )

• decrease in circulating choline esterase levels

decreased circulating serum albumin level ( J:193689 )

decreased circulating total protein level ( J:193689 )

growth/size/body

decreased body weight ( J:193689 )

• at 5 weeks of age, average weight is about 60% of the mean littermate control body weight

behavior/neurological

lethargy ( J:193689 )

hunched posture ( J:193689 )

integument

disheveled coat ( J:193689 )

immune system

intestinal inflammation ( J:193689 )

• lymphocyte infiltration is prominent in both the mucosa and submucosa

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Crohn's disease		DOID:8778		J:193689

Genotype
MGI:6256964

cn2

• Allelic Composition: Pikfyve^tm2.1Tssk/Pikfyve^tm2.1Tssk; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: C57BL/6 * C57BL/6J

Hair greying in tamoxifen-treated Pikfyve^tm2.1Tssk/Pikfyve^tm2.1Tssk Tg(Tyr-cre/ERT2)13Bos/0 mice

pigmentation

abnormal coat/hair pigmentation ( J:262141 )

• after tamoxifen (4-OHT) treatment for 21 days (P28-P50) followed by shave depilation at P50 to induce the 3rd hair cycle, both pigmented and unpigmented hairs are noted at P60, whereas control mice fed a normal diet show fully pigmented hair growth

abnormal hair follicle melanocyte morphology ( J:262141 )

• after 4-OHT treatment (P28-P50) followed by shave depilation at P50, some, but not all, anagen hair follicles (HFs) show a vacuolated phenotype, indicating that Cre-mediated deletion is not 100% efficient; some HFs show normal melanocyte morphology ("normal"), some HFs exhibit accumulation of cells with intracellular vesicles with some residual pigment ("intermediate"), while others show accumulation of cells with intracellular vesicles with little to no pigment ("abnormal")

• EM of skin biopsies taken at P60 show anagen hair bulbs containing melanocytes in various conditions: ~40% appear normal, another ~40% show severe vacuolization exhibiting vesicles within vacuoles resembling multivesicular bodies with very few if any melanosomes, and ~20% show an intermediate phenotype with fewer melanosomes generally of earlier stages

reduced hair shaft melanin granule number ( J:262141 )

• dorsal hairs from 4-OHT-treated mice accumulate ~50% less melanin relative to hairs from control mice at P85, P105, and P365

diluted coat color ( J:262141 )

• after 4-OHT treatment for 29 days (P21-P50) followed by shave depilation of a dorsal region at P50, mice exhibit hair greying with white hairs first seen in the depilated area at P85

• when mice are switched off tamoxifen and fed a normal chow starting at P50, more white hairs are visually apparent at P105

• numerous white hairs accumulate on the head and upper back (areas that have never been shave depilated) by P365, indicating that greying is accelerated but not induced by depilation

• greying is not progressive as mice continue to maintain the same relative level of depigmentation over the course of a year

abnormal endosome to melanosome transport ( J:262141 )

• after DOPA incubation, some of the multivesicular endosome-like structures observed in epidermal melanocytes of 4-OHT-treated mice contain DOPA reaction product, suggesting that TYR may be trapped within this compartment

abnormal melanosome maturation ( J:262141 )

• after 4-OHT treatment, primary melanocytes isolated from newborn mice show a significantly reduced number of pigmented melanosomes per cell relative to vehicle-treated melanocytes

• 4-OHT-treated primary melanocytes exhibit accumulation of full length premelanosome protein (PMEL) relative to vehicle-treated melanocytes

• in culture, some 4-OHT-treated melanocytes accumulate single membrane structures resembling multivesicular endosomes with few stage IV melanosomes, while others accumulate early and late stage melanosomes with a few single membrane structures

integument

abnormal coat/hair pigmentation ( J:262141 )

• after tamoxifen (4-OHT) treatment for 21 days (P28-P50) followed by shave depilation at P50 to induce the 3rd hair cycle, both pigmented and unpigmented hairs are noted at P60, whereas control mice fed a normal diet show fully pigmented hair growth

abnormal hair follicle melanocyte morphology ( J:262141 )

• after 4-OHT treatment (P28-P50) followed by shave depilation at P50, some, but not all, anagen hair follicles (HFs) show a vacuolated phenotype, indicating that Cre-mediated deletion is not 100% efficient; some HFs show normal melanocyte morphology ("normal"), some HFs exhibit accumulation of cells with intracellular vesicles with some residual pigment ("intermediate"), while others show accumulation of cells with intracellular vesicles with little to no pigment ("abnormal")

• EM of skin biopsies taken at P60 show anagen hair bulbs containing melanocytes in various conditions: ~40% appear normal, another ~40% show severe vacuolization exhibiting vesicles within vacuoles resembling multivesicular bodies with very few if any melanosomes, and ~20% show an intermediate phenotype with fewer melanosomes generally of earlier stages

reduced hair shaft melanin granule number ( J:262141 )

• dorsal hairs from 4-OHT-treated mice accumulate ~50% less melanin relative to hairs from control mice at P85, P105, and P365

diluted coat color ( J:262141 )

• after 4-OHT treatment for 29 days (P21-P50) followed by shave depilation of a dorsal region at P50, mice exhibit hair greying with white hairs first seen in the depilated area at P85

• when mice are switched off tamoxifen and fed a normal chow starting at P50, more white hairs are visually apparent at P105

• numerous white hairs accumulate on the head and upper back (areas that have never been shave depilated) by P365, indicating that greying is accelerated but not induced by depilation

• greying is not progressive as mice continue to maintain the same relative level of depigmentation over the course of a year

Genotype
MGI:6256968

cn3

• Allelic Composition: Gt(ROSA)26Sor^{tm4(ACTB-tdTomato,-EGFP)Luo}/Gt(ROSA)26Sor⁺; Pikfyve^tm2.1Tssk/Pikfyve^tm2.1Tssk; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: C57BL/6 * C57BL/6J

Early greying in Pikfyve^tm2.1Tssk/Pikfyve^tm2.1Tssk Tg(Tyr-cre/ERT2)13Bos/0 Gt(ROSA)26Sor^{tm4(ACTB-tdTomato,-EGFP)Luo}/Gt(ROSA)26Sor⁺ mice

pigmentation

diluted coat color ( J:262141 )

• after 4-OHT treatment (P21-P50) mice exhibit an early greying phenotype at P50

• however, GFP+ cells associated with hair follicles are present at P100, indicating that melanocyte survival is not significantly affected

integument

diluted coat color ( J:262141 )

• after 4-OHT treatment (P21-P50) mice exhibit an early greying phenotype at P50

• however, GFP+ cells associated with hair follicles are present at P100, indicating that melanocyte survival is not significantly affected