Phenotypes associated with this allele

• Allele Symbol: Tuft1^{tm1a(KOMP)Wtsi}
• Allele Name: targeted mutation 1a, Wellcome Trust Sanger Institute
• Allele ID: MGI:4419443
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tuft1^tm1a(KOMP)Wtsi/Tuft1^tm1a(KOMP)Wtsi	C57BL/6N-Tuft1^tm1a(KOMP)Wtsi/Wtsi	MGI:5701030
hm2	Tuft1^tm1a(KOMP)Wtsi/Tuft1^tm1a(KOMP)Wtsi	involves: C57BL/6N	MGI:7532607

Genotype
MGI:5701030

hm1

• Allelic Composition: Tuft1^{tm1a(KOMP)Wtsi}/Tuft1^{tm1a(KOMP)Wtsi}
• Genetic Background: C57BL/6N-Tuft1^{tm1a(KOMP)Wtsi}/Wtsi
• Cell Lines: EPD0383_4_H07

Data Sources

IMPC Data for Tuft1

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

homeostasis/metabolism

decreased circulating HDL cholesterol level ( J:211773 )

♂

IMPC - WTSI

decreased circulating alkaline phosphatase level ( J:211773 )

IMPC - WTSI

improved glucose tolerance ( J:211773 )

IMPC - WTSI

integument

abnormal coat appearance ( J:211773 )

IMPC - WTSI

abnormal vibrissa morphology ( J:211773 )

♀

IMPC - WTSI

vision/eye

abnormal eyelid morphology ( J:211773 )

♂

IMPC - WTSI

Genotype
MGI:7532607

hm2

• Allelic Composition: Tuft1^{tm1a(KOMP)Wtsi}/Tuft1^{tm1a(KOMP)Wtsi}
• Genetic Background: involves: C57BL/6N

integument

decreased keratinocyte adhesion ( J:340887 )

• keratinocytes exhibit abnormal cell-cell contacts and impaired intermediate filament (IF) insertion to the desmosome

• intact but free-floating desmosomes without keratin attachment are seen close to the blister fluid, indicating their detachment from the IFs

• KRT5 staining showed a slight nuclear retraction, leaving wider gaps in between cells

waved hair ( J:340887 )

• all mice exhibit a woolly/wavy hair phenotype

abnormal hair shaft morphology ( J:340887 )

• hair displays a groove-like shape, unlike the flattened cylinder shape of wild-type hair

acantholysis ( J:340887 )

acanthosis ( J:340887 )

abnormal epidermis suprabasal layer morphology ( J:340887 )

• wounded skin shows a suprabasal split in the epidermis, with acantholysis and acanthosis

abnormal keratinocyte morphology ( J:340887 )

• keratinocytes exhibit keratin bundle retraction in the proximity of the nucleus

abnormal keratinocyte differentiation ( J:340887 )

• cultured keratinocytes show a significant downregulation of loriscrin and involucrin (late-stage differentiation markers) and an upregulation of desmoplakin, with predominant accumulation of desmoplakin in the cytoplasm

blistering ( J:340887 )

• spontaneous wounds exhibit blister fluid under a thick scab roof

skin lesions ( J:340887 )

• 40% of mice develop spontaneous skin erosions over time due to grooming, scratching and/or fighting, not observed in wild-type controls

increased pruritus ( J:340887 )

• first skin erosion outbursts appear to start a cascade of itching reactions that worsen the phenotype over time

• isolating affected mice or nail cutting does not improve animal welfare

decreased skin tensile strength ( J:340887 )

• 40% of mice develop a mild skin fragility phenotype

cellular

decreased keratinocyte adhesion ( J:340887 )

• keratinocytes exhibit abnormal cell-cell contacts and impaired intermediate filament (IF) insertion to the desmosome

• intact but free-floating desmosomes without keratin attachment are seen close to the blister fluid, indicating their detachment from the IFs

• KRT5 staining showed a slight nuclear retraction, leaving wider gaps in between cells

abnormal keratinocyte differentiation ( J:340887 )

• cultured keratinocytes show a significant downregulation of loriscrin and involucrin (late-stage differentiation markers) and an upregulation of desmoplakin, with predominant accumulation of desmoplakin in the cytoplasm

homeostasis/metabolism

wounding ( J:340887 )

cardiovascular system

cardiovascular system phenotype ( J:340887 )

N • although TUFT1 is specifically localized at the intercalated discs of the myocardium in wild-type controls, no cardiac abnormalities are observed up to 12 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
palmoplantar keratosis		DOID:3390		J:340887