Phenotypes Associated with This Genotype

Genotype
MGI:3700128

• Allelic Composition: Alms1^L2131X/Alms1^L2131X
• Genetic Background: involves: C57BL/6 * NOD

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

Kidney abnormalities of Alms1^L2131X/Alms1^L2131X mice at 6 months of age

growth/size/body

increased susceptibility to weight gain ( J:118221 )

• mutants gain weight faster than controls between weeks 7 and 10

homeostasis/metabolism

increased circulating insulin level ( J:118221 )

• most older mice have normal glucose levels with hyperinsulinemia

increased circulating leptin level ( J:118221 )

• mice display elevated leptin levels

abnormal circulating cholesterol level ( J:118221 )

increased circulating HDL cholesterol level ( J:118221 )

increased circulating triglyceride level ( J:118221 )

increased urine protein level ( J:118221 )

• a mild proteinuria is detected at 6 months of age

renal/urinary system

abnormal renal tubule epithelial cell primary cilium morphology ( J:118221 )

• at 6 months of age, most proximal (LTA-labeled) tubule cells are not ciliated, in contrast to wild-type controls

• however, aquaporin-2-labeled collecting duct cells exhibit clear primary cilia as expected

increased kidney apoptosis ( J:118221 )

• kidney epithelial cell apoptosis is markedly increased at 6 months

increased kidney cell proliferation ( J:118221 )

• at 6 months of age, increased levels of proliferation are detected in the kidney cortex, unlike in wild-type kidneys

• in most cross sections of dilated tubules, 20%-50% of the epithelial cells are Ki67-positive and lack primary cilia

increased urine protein level ( J:118221 )

• a mild proteinuria is detected at 6 months of age

abnormal proximal convoluted tubule morphology ( J:118221 )

• at 6 months of age, most proximal (LTA-labeled) tubules in mutants are not ciliated, in contrast to wild-type controls

dilated renal tubule ( J:118221 )

• at 6 months of age, mice exhibit multiple dilated tubules in the cortex

adipose tissue

increased total body fat amount ( J:118221 )

• weight gain observed in homozygotes is due almost entirely to increase in fat mass

increased fat cell size ( J:118221 )

• white and brown adipocytes display hypertrophy

liver/biliary system

hepatic steatosis ( J:118221 )

• mice show steatosis

reproductive system

seminiferous tubule degeneration ( J:118221 )

♂

abnormal spermatogenesis ( J:118221 )

♂ • males have defective sperm formation in the testes

vision/eye

abnormal eye physiology ( J:118221 )

• mice have defective rhodopsin transport in the retina

endocrine/exocrine glands

seminiferous tubule degeneration ( J:118221 )

♂

cellular

abnormal renal tubule epithelial cell primary cilium morphology ( J:118221 )

• at 6 months of age, most proximal (LTA-labeled) tubule cells are not ciliated, in contrast to wild-type controls

• however, aquaporin-2-labeled collecting duct cells exhibit clear primary cilia as expected

increased kidney apoptosis ( J:118221 )

• kidney epithelial cell apoptosis is markedly increased at 6 months

increased kidney cell proliferation ( J:118221 )

• at 6 months of age, increased levels of proliferation are detected in the kidney cortex, unlike in wild-type kidneys

• in most cross sections of dilated tubules, 20%-50% of the epithelial cells are Ki67-positive and lack primary cilia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alstrom syndrome		DOID:0050473	OMIM:203800	J:118221