Phenotypes Associated with This Genotype

Genotype
MGI:8246765

• Allelic Composition: Mvk^{Gt(OST201716)Lex}/Mvk⁺
• Genetic Background: involves: 129S5/SvEvBrd * C57BL/6

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

behavior/neurological

decreased aggression ( J:371688 )

• mice appear docile and nonaggressive from birth throughout at least 48 weeks

decreased locomotor activity ( J:371688 )

• movement is slowed down by 12 weeks of age

cellular

abnormal erythrocyte basophilic stippling ( J:371688 )

• overt basophilic stippling of the red blood cells is seen suggesting anemia

digestive/alimentary system

intestine polyps ( J:371688 )

• about 20% of mice that are sacrificed between 20 and 40 weeks of age have at least one sizable intestinal polyp in the large bowel

growth/size/body

enlarged liver ( J:371688 )

• about 25% of mice that are sacrificed between 20 and 40 weeks of age have hepatomegaly with some livers almost doubled in size

enlarged spleen ( J:371688 )

• about 1/3 of mice that are sacrificed between 20 and 40 weeks of age have splenomegaly with spleen sizes ranging 3-4 times larger than wild-type

hematopoietic system

abnormal erythrocyte basophilic stippling ( J:371688 )

• overt basophilic stippling of the red blood cells is seen suggesting anemia

enlarged spleen ( J:371688 )

• about 1/3 of mice that are sacrificed between 20 and 40 weeks of age have splenomegaly with spleen sizes ranging 3-4 times larger than wild-type

decreased bone marrow cell number ( J:371688 )

• bone marrow is hypocellular with an erythroid dominance and dysplastic megakaryocytes in mice that are sacrificed between 20 and 40 weeks of age

abnormal megakaryocyte morphology ( J:371688 )

• bone marrow shows dysplastic megakaryocytes in mice that are sacrificed between 20 and 40 weeks of age

decreased neutrophil cell number ( J:371688 )

• severe neutropenia with white blood cell differential averages of 74% atypical lymphocytes and 26% monocytes is seen in mice that are sacrificed between 20 and 40 weeks of age

abnormal IgA level ( J:371688 )

• mice show a trend towards higher IgA levels in sera

increased IgD level ( J:371688 )

• IgD levels are increased 9-12-fold in sera in both young (less than 15 weeks) and older (greater than 15 weeks) mice

homeostasis/metabolism

abnormal homeostasis ( J:371688 )

• mevalonate concentrations in 6-week-old mice are increased in the spleen, heart, and kidney but are normal in brain and liver

• however, cholesterol levels in tissues and blood, and isoprene end-products (ubiquinone, dolichol) in tissues are normal

increased circulating tumor necrosis factor level ( J:371688 )

• mice show increased serum TNF-alpha levels, but there is wide variation in levels between individual mice that the difference in means is not statistically significant

abnormal body temperature homeostasis ( J:371688 )

• 12-week-old females show increased body temperature of about one degree higher than in wild-type mice and temperature rhythmicity patterns have an average periodicity of 0.9 min compared to 0.5 min in wild-type mice, indicating a slower fluctuation frequency almost twice as long as that of wild-type mice

abnormal enzyme/coenzyme activity ( J:371688 )

• 8-week-old mice show reduced liver mevalonate kinase enzyme activity

immune system

immune system phenotype ( J:371688 )

N • inguinal lymph nodes are not enlarged

enlarged spleen ( J:371688 )

• about 1/3 of mice that are sacrificed between 20 and 40 weeks of age have splenomegaly with spleen sizes ranging 3-4 times larger than wild-type

decreased neutrophil cell number ( J:371688 )

• severe neutropenia with white blood cell differential averages of 74% atypical lymphocytes and 26% monocytes is seen in mice that are sacrificed between 20 and 40 weeks of age

abnormal IgA level ( J:371688 )

• mice show a trend towards higher IgA levels in sera

increased IgD level ( J:371688 )

• IgD levels are increased 9-12-fold in sera in both young (less than 15 weeks) and older (greater than 15 weeks) mice

increased circulating tumor necrosis factor level ( J:371688 )

• mice show increased serum TNF-alpha levels, but there is wide variation in levels between individual mice that the difference in means is not statistically significant

integument

abnormal coat appearance ( J:371688 )

• coats are dull by 12 weeks of age

ruffled hair ( J:371688 )

• coats are ruffled by 12 weeks of age

liver/biliary system

enlarged liver ( J:371688 )

• about 25% of mice that are sacrificed between 20 and 40 weeks of age have hepatomegaly with some livers almost doubled in size

skeleton

fragile skeleton ( J:371688 )

• femurs are brittle in mice that are sacrificed between 20 and 40 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hyperimmunoglobulinemia D periodic fever syndrome		DOID:0081450	OMIM:260920	J:371688