Phenotypes associated with this allele

• Allele Symbol: Lepr^db-5J
• Allele Name: diabetes 5 Jackson
• Allele ID: MGI:2683234
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lepr^db-5J/Lepr^db-5J	NOD/ShiLtJ-Lepr^db-5J/LtJ	MGI:2684204
hm2	Lepr^db-5J/Lepr^db-5J	NOD/ShiLt-Lepr^db-5J	MGI:3699232
ht3	Lepr^db/Lepr^db-5J	involves: C57BLKS/J * NOD/ShiLtJ	MGI:3699233

Genotype
MGI:2684204

hm1

• Allelic Composition: Lepr^db-5J/Lepr^db-5J
• Genetic Background: NOD/ShiLtJ-Lepr^db-5J/LtJ

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

endocrine/exocrine glands

degranulated pancreatic beta cells ( J:87061 )

• beta-degranulation in the islets of Langerhans

pancreatic islet hyperplasia ( J:87061 )

growth/size/body

obese ( J:87061 )

• both males and females are obese by weaning age

homeostasis/metabolism

hyperglycemia ( J:87061 )

• age of onset by 5 weeks

increased circulating insulin level ( J:87061 )

Genotype
MGI:3699232

hm2

• Allelic Composition: Lepr^db-5J/Lepr^db-5J
• Genetic Background: NOD/ShiLt-Lepr^db-5J

mortality/aging

premature death ( J:118305 )

• 3/6 males showing weight loss with severe hyperglycemia die by 41-49 weeks of age

• mice with juvenile-onset hyperglycemia did not require insulin therapy to survive to >39 weeks, whereas wild-type NOD littermates developed adult onset hyperglycemia, rapidly lost weight, and were euthanized

growth/size/body

weight loss ( J:118305 )

• 35.3% (6/17) homozygous males show a persistent decrease in weight beginning at 7-9 weeks and continuing to 39 weeks of age

increased susceptibility to weight gain ( J:118305 )

• within 1 week of weaning, mice gain 6-10 grams more than wild-type littermates

• females show rapid weight gain up ~15 weeks of age to a ~stable weight of 40 grams

• males also show marked weight gain after weaning; in 64.7% of males (11/17), postpubertal (from 7 weeks of age) weight gain continues

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:118304 )

N • plasmacorticosterone levels in mutants and NOD controls are similar

abnormal circulating glucose level ( J:118305 )

• hyperglycemia in all females and subset of males remits to normoglycemia with increasing age, while lean littermates show progression to type I diabetes

• 4/11 males showing maintained elevated body weight become normoglycemic (glucose 145 mg/dl at 39 weeks); remaining 7 males in this group are still hyperglycemic but exhibit lower mean blood glucose level (386 mg/dl) at 39 weeks

hyperglycemia ( J:118305 )

• develops in most obese mice withing 2 weeks of weaning

• the males (6/17) showing decrease in body weight display severe hyperglycemia (glucose 581 mg/dl at 39 weeks)

• by 5-7 weeks of age, 4/5 females and 11/17 males are hyperglycemic (glucose >200 mg/dl) and most remain hyperglycemic through the peripubertal period (253-686 mg/dl at 13 weeks)

increased circulating insulin level ( J:118305 )

• levels increase markedly above lean controls with age

• females remitting to normoglycemia still exhibit elevated insulin levels; males showing weight loss display reduced insulin levels (~nondiabetic control), while males maintaining elevated weight still show elevated levels

increased circulating leptin level ( J:118305 )

• levels increase markedly above lean controls with age

• females remitting to normoglycemia still exhibit elevated leptin levels

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:118305 )

• animals that maintained high body weight with or without remission from intermediate levels of hyperglycemia have extremely hyperplastic islets with well-granulated beta cells; islets display peri-insulitis

• males exhibiting unrestrained hyperglycemia and weight loss have islets reduced in size and number of granulated beta cells, but showing minimal intraislet insulitis

degranulated pancreatic beta cells ( J:118305 )

• islets are normal-sized with markedly degranulated beta cells

pancreas inflammation ( J:118305 )

• perivascular/periductular infiltrates are present but nor intraislet infiltrates are observed

periinsulitis ( J:118305 )

behavior/neurological

polyphagia ( J:118305 )

• early weight gain is associated with hyperphagia; at 5 weeks, mice consume twice as much as lean controls

adipose tissue

increased percent body fat/body weight ( J:118305 )

• at 15 weeks, females have 40.5% carcass fat vs 19.9% in lean littermates; males show 33% body fat vs 14.7% in lean males

immune system

pancreas inflammation ( J:118305 )

• perivascular/periductular infiltrates are present but nor intraislet infiltrates are observed

periinsulitis ( J:118305 )

abnormal CD4-positive, alpha beta T cell morphology ( J:118304 )

• CD4+ CD25+ T cells are slightly reduced in percentage compared to control NOD/LtJ mice (8.0 vs 9.5%)

abnormal CD8-positive, alpha beta T cell morphology ( J:118304 )

• beta cell autoreactive CD8+ T cell clonotypes are decreased in mutants compared to NOD controls; IGRP and insulin-reactive CD8+ clonotypes are 5.7- and 1.7-fold lower in spleens of female mutants compared to controls

hematopoietic system

abnormal CD4-positive, alpha beta T cell morphology ( J:118304 )

• CD4+ CD25+ T cells are slightly reduced in percentage compared to control NOD/LtJ mice (8.0 vs 9.5%)

abnormal CD8-positive, alpha beta T cell morphology ( J:118304 )

• beta cell autoreactive CD8+ T cell clonotypes are decreased in mutants compared to NOD controls; IGRP and insulin-reactive CD8+ clonotypes are 5.7- and 1.7-fold lower in spleens of female mutants compared to controls

Genotype
MGI:3699233

ht3

• Allelic Composition: Lepr^db/Lepr^db-5J
• Genetic Background: involves: C57BLKS/J * NOD/ShiLtJ

growth/size/body

obese ( J:118305 )

• 25% of offspring exhibit obesity