Phenotypes associated with this allele

• Allele Symbol: Ctns^tm1Antc
• Allele Name: targeted mutation 1, Corinne Antignac
• Allele ID: MGI:2388945
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ctns^tm1Antc/Ctns^tm1Antc	involves: 129/Sv * C57BL/6	MGI:2672886

Genotype
MGI:2672886

hm1

• Allelic Composition: Ctns^tm1Antc/Ctns^tm1Antc
• Genetic Background: involves: 129/Sv * C57BL/6

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

pigmentation

abnormal retina pigmentation ( J:79610 )

• the severely impaired ERG correlated with patches of depigmentation in the peripheral retina, suggesting that impaired visual function could lead to blindness in time

behavior/neurological

increased anxiety-related response ( J:79610 )

• lack of movement at the beginning of the open-field test, continual wall hugging, and a reduction in overall activity indicated an increase in anxiety

increased thigmotaxis ( J:79610 )

decreased locomotor activity ( J:79610 )

• at around 6 months of age, homozygotes showed reduced motility in the open-field test

cellular

dilated mitochondrion ( J:79610 )

• mitochondrial swelling was focally observed in the proximal tubular cells of homozygous mutant mice

homeostasis/metabolism

increased cysteine level ( J:79610 )

• homozygotes displayed accumulation of cystine in all tissues tested; cystine levels increased with age

• at one year of age, cystine levels in liver, kidney, and muscle increased by factors of 1,350, 413, and 120, respectively

• cystine crystals were observed in the interstitial cells and macrophages of most organs

• cystine crystal accumulation was moderate relative to human patients with infantile cystinosis, and remained stable from 8 to 18 months in the absence of severe consequences

muscle

muscle degeneration ( J:79610 )

• cystine crystals were observed in muscle interstitial cells and were associated with foci of myocyte necrosis in 1/4 of mutants examined

• creatine phosphokinase (CPK) levels were significantly elevated in some mutants, suggesting muscular impairment

renal/urinary system

renal/urinary system phenotype ( J:79610 )

N • despite high cystine accumulation in the kidney, homozygotes showed no signs of proximal tubulopathy or renal failure, even at 18 months of age

N • the lack of proximal tubulopathy in mutant mice constitutes a major difference from the infantile form of human cystinosis

skeleton

decreased bone mineral density ( J:79610 )

• homozygotes exhibited bone demineralization of the vertebrae and long bones

decreased compact bone thickness ( J:79610 )

• homozygotes showed cortical thinning of the vertebrae and long bones

vision/eye

abnormal retina pigmentation ( J:79610 )

• the severely impaired ERG correlated with patches of depigmentation in the peripheral retina, suggesting that impaired visual function could lead to blindness in time

corneal deposits ( J:79610 )

• at 8 months, all four mutants examined had corneal cystine crystal deposits

abnormal eye electrophysiology ( J:79610 )

• the electroretinogram (ERG) was normal in two homozygotes, "supernormal" in one, and impaired in the other

• the "supernormal" ERG may result from the dispersion of light by the refractile crystals in the cornea (Tyndall's effect), which could generate stronger retinal stimuli and increase the ERG response

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cystinosis		DOID:1064	OMIM:219750 OMIM:219800 OMIM:219900	J:79610