Phenotypes Associated with This Genotype

Genotype
MGI:2175824

• Allelic Composition: Ctsl^tm1Cptr/Ctsl^tm1Cptr
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:70118 )

• up to weaning, homozygotes exhibit increased postnatal mortality relative to wild-type mice (15% vs 6%, respectively)

• thereafter, a normal mortality rate is observed for an interval of greater than 50 weeks

endocrine/exocrine glands

abnormal thyroid gland morphology ( J:83877 )

• cells with enlarged lysosomes

homeostasis/metabolism

amyloidosis ( J:116135 )

• significantly smaller amounts of amyloid deposited in the spleen

• amyloid deposits of full sized protein

abnormal thyroid hormone level ( J:83877 )

• 5-6 fold increases in thyroglobulin levels

decreased thyroxine level ( J:83877 )

• significantly reduced levels of T4

hematopoietic system

increased regulatory T cell number ( J:153355 )

• mice exhibit an increase in Foxp3-expressing T cells

immune system

increased regulatory T cell number ( J:153355 )

• mice exhibit an increase in Foxp3-expressing T cells

integument

increased keratinocyte proliferation ( J:70118 )

• homozygotes display hyperproliferation of basal epidermal keratinocytes while the number of apoptotic cells in the epidermis remains unaffected

alopecia ( J:70118 )

• homozygotes start to lose their fur at P21, beginning at the head and progressing toward the tail region of the back, until they are almost nude at P28-P30

• a new coat starts to grow during the onset of the anagen phase, followed by a new wave of spatially restricted hair loss at 7 weeks

• mature homozygotes are always partially devoid of hair

delayed hair appearance ( J:70118 )

• appearance of the first pelage fur is delayed by 2 days

abnormal hair shaft morphology ( J:70118 )

• at P6, mutant hair shafts are significantly shorter and not yet emerging through the skin; however, hair follicle density is normal

abnormal hair follicle development ( J:70118 )

• at P6, homozygous neonates exhibit delayed hair follicle morphogenesis

underdeveloped hair follicles ( J:70118 )

• at P6, wild-type mice display 51.4% stage 7 and 48.6% stage 8 hair follicles, whereas homozygotes exhibit 84.4% of hair follicles in stage 7 of hair follicle morphogenesis

hair follicle outer root sheath hyperplasia ( J:70118 )

• at ~P20 (during hair follicle regression), the outer root sheath displays significant hyperplasia

dilated piliary canal ( J:70118 )

• at P20, mutant hair follicles display a pathological disintegration of the developing club hair; as a result, the hair canal is distended

absent vibrissae ( J:70118 )

• no vibrissae are identified at birth

abnormal hair cycle ( J:70118 )

• homozygotes exhibit a significant delay in catagen progression as well as premature entry into anagen

• at P20, 95% of wild-type hair follicles are in catagen stages VII or VIII, whereas mutant hair follicles are predominantly in catagen VI (35.2%) and VII (46.3%)

• at P28, 69% of wild-type hair follicles are in telogen, whereas all mutant hair follicles have already prematurely entered anagen (anagen V or VI) of the first hair cycle

thick dermal layer ( J:70118 )

• at P14, the mutant back skin exhibits drastic thickening of the dermis

abnormal epidermis stratum basale morphology ( J:70118 )

• homozygotes display hyperproliferation of hair follicle epithelial cells and basal epidermal keratinocytes

hyperkeratosis ( J:70118 )

• hyperkeratosis is observed in the epidermis of back and tail skin of 3-month-old mutant mice

acanthosis ( J:70118 )

• acanthosis is observed in the epidermis of back and tail skin of 3-month-old mutant mice

epidermal hyperplasia ( J:70118 )

• hyperplasia is observed in the epidermis of back and tail skin of 3-month-old mutant mice

thick epidermis ( J:70118 )

• as early as P6, the mutant epidermis is already slightly thickened; no thickening is noted at P3

• at P20, the mutant skin still maintains the thickness of late catagen stages

• epidermal thickening is caused by hyperproliferation of basal keratinocytes

scaly skin ( J:70118 )

• at P7-P9, the skin of homozygotes has a squamous appearance

shiny skin ( J:70118 )

• at P7-P9, the skin of homozygotes has a shiny appearance

thick skin ( J:70118 )

cellular

increased keratinocyte proliferation ( J:70118 )

• homozygotes display hyperproliferation of basal epidermal keratinocytes while the number of apoptotic cells in the epidermis remains unaffected

renal/urinary system

renal/urinary system phenotype ( J:172774 )

N • normal kidney morphology is obseved

N • no cellular disorganization or enlargement of nuclei is seen in kidney proximal tubular cells