Phenotypes Associated with This Genotype

Genotype
MGI:3664785

• Allelic Composition: Grm1^crv4/Grm1^crv4
• Genetic Background: BALB/cPas-Grm1^crv4

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

growth/size/body

decreased body size ( J:112290 )

• mice homozygous for this mutation are one-third smaller than littermates from birth

behavior/neurological

tremors ( J:112290 )

• homozygous mutant mice exhibit whole body tremor during movement

ataxia ( J:112290 )

• footprint analysis shows that homozygous mutant mice exhibit a pronounced wide-base, side-to-side rolling gait, with their feet sweeping the floor, and they cannot walk in a straight line

muscle

muscle spasm ( J:112290 )

• homozygous mutant mice exhibit mild hindlimb spasticity

reproductive system

reduced female fertility ( J:112290 )

♀ • fertility of homozygous female mice is greatly reduced

male infertility ( J:112290 )

♂ • homozygous males seem to be sterile

skeleton

kyphoscoliosis ( J:112290 )

• the dorsal thorax of homozygous mice, particularly of females, often protrudes prominently; X-radiography and, upon necropsy at 6-8 months of age, alizarin red/alcian blue staining of the skeleton reveal thoracic kyphoscoliosis in affected mice

adipose tissue

increased brown adipose tissue amount ( J:112290 )

• homozygous mutant mice often have increased amounts of interscapular brown fat, in some females almost twice the amount present in wild-type female mice

vision/eye

narrow eye opening ( J:112290 )

• one or both eyes of homozygous mutant mice appear more closed than those of wild-type mice; examination of sectioned eyes reveals no obvious abnormalities

renal/urinary system

albuminuria ( J:169685 )

• homozygotes show a 3-fold increase in mean urinary albumin excretion (UAE) values relative to wild-type controls

• albuminuria progresses with increasing age, ranging from low levels (UAE range, 8.95 to 221.51 ug/mg) at 2-6 months of age to higher values at >6 months (UAE range, 55.27 to 423.65 ug/mg), unlike in wild-type controls where values remain constant (UAE range at 2-6 months, 5.62 to 57.21 ug/mg; UAE range at >6 months, 8.80 to 60.12 ug/mg)

abnormal podocyte morphology ( J:169685 )

• by 8 months of age, homozygotes exhibit diffuse progressive loss of nephrin and synaptopodin, and segmental loss of podocin and ZO-1 relative to wild-type controls

• in culture, primary podocytes display progressive loss of nephrin expression, and remodeling of actin filaments with loss of stress fibers and increased peripheral actin distribution

podocyte foot process effacement ( J:169685 )

• as early as 2 months of age, homozygotes exhibit diffuse foot process effacement, unlike wild-type controls

• more severe foot process effacement is noted at 8 months

• homozygotes show a progressive increase in mean foot process width (FPW), defined as the width of one foot process and the adjacent filtration slit, relative to wild-type controls

abnormal renal glomerulus basement membrane morphology ( J:169685 )

• at 2 months of age, homozygotes exhibit a convoluted and thickened GBM, unlike wild-type controls

• more severe GBM changes are noted at 8 months

increased renal glomerulus basement membrane thickness ( J:169685 )

• at 2 months of age and becoming more severe at 8 months

glomerulosclerosis ( J:169685 )

• following i.v. injection of a low dosage of adriamycin (8 mg/kg body weight), 8-month-old homozygotes exhibit glomerular damage with signs of segmental or global glomerulosclerosis, unlike similarly-treated control mice

abnormal proximal convoluted tubule morphology ( J:169685 )

• at 2 months of age, protein and lipid accumulation is detected in the proximal tubular cells, unlike in wild-type controls

renal cast ( J:169685 )

• at 2 months of age, protein accumulation is detected in the proximal tubular cells, unlike in wild-type controls

• at 4-8 months of age, renal tubuli are filled with dense material that stains positive by an antibody against mouse albumin

• following i.v. injection of a low dosage of adriamycin (8 mg/kg body weight), 8-month-old homozygotes exhibit tubular protein casts, unlike similarly-treated control mice

abnormal glomerular filtration barrier function ( J:169685 )

• at 7 months of age, homozygotes a show a significant increase in the mean glomerular permeability to albumin (Palb) value relative to wild-type controls

homeostasis/metabolism

albuminuria ( J:169685 )

• homozygotes show a 3-fold increase in mean urinary albumin excretion (UAE) values relative to wild-type controls

• albuminuria progresses with increasing age, ranging from low levels (UAE range, 8.95 to 221.51 ug/mg) at 2-6 months of age to higher values at >6 months (UAE range, 55.27 to 423.65 ug/mg), unlike in wild-type controls where values remain constant (UAE range at 2-6 months, 5.62 to 57.21 ug/mg; UAE range at >6 months, 8.80 to 60.12 ug/mg)

increased susceptibility to injury ( J:169685 )

• following injection of a low dosage of adriamycin (8 mg/kg body weight), homozygotes exhibit tubular protein casts, damaged glomeruli with signs of segmental or global sclerosis, and increased cellularity (likely due to inflammatory cells), unlike similarly-treated control mice

nervous system

nervous system phenotype ( J:112290 )

N • no gross morphological anomalies were observed in the cerebellum, hippocampus or other brain regions of homozygous mutant mice

N • Purkinje cell numbers, size and distribution in brains of homozygous mutants appear normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive spinocerebellar ataxia 13		DOID:0080062	OMIM:614831	J:112290