Phenotypes associated with this allele

• Allele Symbol: Arsb^tm1Cptr
• Allele Name: targeted mutation 1, Christoph Peters
• Allele ID: MGI:2180365
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Arsb^tm1Cptr/Arsb^tm1Cptr	involves: 129P2/OlaHsd * 129S2/SvPas	MGI:3712734
hm2	Arsb^tm1Cptr/Arsb^tm1Cptr	involves: 129P2/OlaHsd * C57BL/6J	MGI:2655540

Genotype
MGI:3712734

hm1

• Allelic Composition: Arsb^tm1Cptr/Arsb^tm1Cptr
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas

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

cellular

abnormal cell morphology ( J:102290 )

• 4- to 15-fold increase of glycosaminoglycan content in tissues of 6-month-old mice

cardiovascular system

abnormal heart valve morphology ( J:102290 )

• heart valves show considerable thickening

thick mitral valve ( J:102290 )

• mitral valve thickening is detected by echocardiography in 4 of 10 mutants

heart valve hyperplasia ( J:102290 )

• leaflets shows an enlargement of cells that contain vacuoles and a higher cell number

decreased cardiac output ( J:102290 )

• the cardiac output is almost half of wild-type

decreased cardiac muscle contractility ( J:102290 )

• fractional shortening of the myocardium is reduced to about 2/3 of wild-type

• the left ventricular diameter at the end of systole is enlarged while the left ventricular diameter at the end of diastole is not changed

mitral valve regurgitation ( J:102290 )

• 2 of the 4 mutants with mitral valve thickening show mitral regurgitation

decreased systemic arterial blood pressure ( J:102290 )

• the systolic and diastolic functional properties of hearts are severely impaired

• significantly lower velocity of blood flow and reduction in pressure gradients across the aortic and mitral valves

• impaired diastolic properties are shown by a reduction of the Vmax of the mitral E-wave of 38% representing the impaired diastolic filling of the left ventricle

vision/eye

abnormal cornea morphology ( J:102290 )

• exhibit corneal alterations that range from mild disarrangement of fibrils to severe stromal disarray with large fissures

• however, homozygotes do not develop corneal clouding as is frequently observed in MPS VI patients

abnormal corneal epithelium morphology ( J:102290 )

• in most cases, corneal epithelium shows reduced thickness and loss of the typical cell alignment

decreased corneal epithelium thickness ( J:102290 )

disorganized corneal epithelium ( J:102290 )

muscle

decreased cardiac muscle contractility ( J:102290 )

• fractional shortening of the myocardium is reduced to about 2/3 of wild-type

• the left ventricular diameter at the end of systole is enlarged while the left ventricular diameter at the end of diastole is not changed

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mucopolysaccharidosis VI		DOID:12800	OMIM:253200	J:102290

Genotype
MGI:2655540

hm2

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

Skeletal abnormalities of the Arsb^tm1Cptr/Arsb^tm1Cptr mouse

craniofacial

increased cranium width ( J:34831 )

• biparietal diameter of the skull is enlarged starting around 4 weeks of age

short maxilla ( J:34831 )

short snout ( J:34831 )

• animals develop a short snout after 4 weeks of age

broad head ( J:34831 )

• broadened head becomes obvious around 4 weeks of age

growth/size/body

short snout ( J:34831 )

• animals develop a short snout after 4 weeks of age

broad head ( J:34831 )

• broadened head becomes obvious around 4 weeks of age

decreased body weight ( J:34831 )

• 15% reduction in body weight at 9-12 months of age

homeostasis/metabolism

increased urine glycosaminoglycan level ( J:34831 )

• elevated glycosaminoglycans in the urine

limbs/digits/tail

increased autopod size ( J:34831 )

• animals develop rough, broadened paws after 4 weeks of age

short limbs ( J:34831 )

• animals develop shortened limbs after 4 weeks of age

renal/urinary system

increased urine glycosaminoglycan level ( J:34831 )

• elevated glycosaminoglycans in the urine

skeleton

increased cranium width ( J:34831 )

• biparietal diameter of the skull is enlarged starting around 4 weeks of age

short maxilla ( J:34831 )

decreased length of long bones ( J:34831 )

• long bones are shortened and broadened

abnormal pelvic girdle bone morphology ( J:34831 )

• pelvic abnormality

abnormal rib morphology ( J:34831 )

• ribs exhibit thickening and wavy, irregular surfaces

abnormal cartilage morphology ( J:34831 )

• irregular structure, thickened cartilage

• cartilaginous anlagen of vertebrae as well as skull exhibit a perturbed structure and an irregular surface and contain ballooned chondroctyes

abnormal tracheal cartilage morphology ( J:34831 )

• at 4 weeks of age, tracheal cartilages are thickened and exhbiit an irregular structure with ballooned, vacuolated chondrocytes

disorganized long bone epiphyseal plate ( J:34831 )

• growth plates of long bones are highly broadened at 4 weeks of age, the columnar arrangement of chondrocytes is lost, and ballooned and vaculolated chondrocytes are found not only in the opening zone as in wild-type but also across the longitudinal extension of growth plates

increased long bone epiphyseal plate size ( J:34831 )

• growth plates of long bones are highly broadened at 4 weeks of age, the columnar arrangement of chondrocytes is lost, and ballooned and vaculolated chondrocytes are found not only in the opening zone as in wild-type but also across the longitudinal extension of growth plates

abnormal articular cartilage morphology ( J:34831 )

• at 4 weeks of age, articular cartilages are thickened and exhibit an irregular structure with ballooned, vacuolated chondroctyes

hematopoietic system

abnormal blood cell morphology/development ( J:34831 )

• in blood smears, coarse granular inclusion bodies similar to Alder-Reilly bodies in human MPS VI are seen in almost all polymorphonuclear leukocytes and in about 50% of lymphocytes

respiratory system

abnormal tracheal cartilage morphology ( J:34831 )

• at 4 weeks of age, tracheal cartilages are thickened and exhbiit an irregular structure with ballooned, vacuolated chondrocytes

cellular

abnormal cell morphology ( J:34831 )

• storage of glycosaminoglycans is observed in the liver, lung, kidney, blood vessels, spleen, trachea, esophagus, stomach, small and large intestine, pancreas, salivary gland, testis, skin, adrenal gland, and lymph nodes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mucopolysaccharidosis VI		DOID:12800	OMIM:253200	J:34831