Additional selected JAX® Mice models for metabolic research

Some of the following strains are not necessarily models but may be used as “tools” in diabetes & obesity research

A/J

000646

  • Whether fed chow, high-fat, or a high cholesterol-containing diet, this strain is resistant to diabetes and obesity (Surwit et al. 1995; Rossmeisl et al. 2003).
  • One of the lowest glucose levels of all inbred mouse strains

ALR/LtJ and ALS/LtJ

003070 and 003072

  • Useful for a variety of diabetes- and obesity-related research, including type 1 diabetes, type 2 diabetes, islet transplantation, adult-onset moderate obesity without diabetes, metabolism, and toxicology research
  • Alloxan-untreated ALS/LtJ mice become obese and extremely hyperinsulinemic; males becoming progressively glucose intolerant; subset of these males develops spontaneous type 2 diabetes that responds to anti-oxidant therapy (Mathews et al. 2004)
  • ALR/LtJ mice have normal glucose tolerance but gain weight rapidly (females weigh as much as males do by 50 weeks); may be used as controls for ALS/LtJ mice; genetically very similar to type 1 diabetes-prone NOD/ShiLtJ mice but are very resistant to autoimmune type 1 diabetes, partly because they have unusually strong systemic defenses against the generation of free radicals (Graser et al. 1999; Mathews et al. 2001, 2002).

B6.129S7-Ldlrtm1Her/J

002207

  • Males fed diabetogenic high-fat diets exhibit metabolic syndrome phenotypes: hypertriglyceridemia, hypercholesterolemia, hyperleptinemia, hyperinsulinemia, moderate hyperglycemia, obesity, high vascular calcification, atherosclerosis, and high free fatty acid levels (Merat et al. 1999; Schreyer et al. 2002; Towler et al. 1998)
  • May also be used as a diet-induced obesity (DIO) model

B6.Cg- Ay/J

000021

B6(Cg)-Tubtub/J

000562

  • Homozygotes develop maturity-onset obesity, recognizable at three to four months in males and at four to six months in females
  • Although plasma insulin rises before obvious signs of obesity and may be 20 times higher than normal in six-month olds, tubby mice do not become diabetic
  • High HDL levels, resistant to diet-induced atherosclerosis
  • Retinal degeneration and progressive hearing loss (Nishina et al. 1994; Noben-Trauth et al. 1996)
  • Both sexes fertile

B6.HRS(BKS)-Cpefat/J

003923

  • Diabetes in homozygotes characterized by hyperglycemia and insulin resistance
  • Becomes obese earlier and appears healthier (no hydronephrosis, fewer malocclusions) than BKS.HRS-Cpefat/J
  • Females become heavier than males
  • Both sexes become obese later than B6.Cg-Lepob/J (000632) and BKS.Cg-Dock7m +/+ Leprdb/J (000642) (Walker and Truett 1997).
  • Two modifier loci (Mobe1, Mobe2, formerly called Moo1 and Moo2) regulate total fat mass: BTBR alleles of these loci semi-dominantly increase body mass (Clee et al. 2005)

Ins2Akita mutants

Ins2Akita mutants are suitable for a wide variety of diabetes- and obesity-related research, including hyperglycemia, hypoinsulinemia, impaired insulin processing, insulin receptors and growth factors, islet transplantation, mature onset of type 1 diabetes in young mice, and pancreas defects.

C57BL/6-Ins2Akita/J

003548

  • Models non-obese, early onset type 2 diabetes of autosomal dominant inheritance
  • Untreated homozygotes rarely live past 12 weeks; heterozygotes viable and fertile
  • Diabetes characterized by hyperglycemia, hypoinsulinemia, polydipsia, and polyuria by three to four weeks
  • Insulitis-free symptoms more severe and progressive in males
  • Mean lifespan of diabetic males is 305 days, significantly shorter than that of nondiabetics (690 days)
  • Mortality rates of diabetic and nondiabetic females comparable
  • Heterozygotes have few islets with relatively few beta cells (release very little mature insulin) but respond to exogenously administered insulin, indicating that Ins2Akita mice are an excellent substitute for mice made insulin-dependent-diabetic with alloxan or streptozotocin
  • Heterozygotes do not need to be treated with a diabetogen to induce hyperglycemia, hence ideally suited to syngenic islet transplantation (Mathews et al. 2002)
  • Because heterozygotes survive a long time with chronic hyperglycemia without insulin therapy, they are used to study the development of diabetic complications, most notably diabetic neuropathy and nephropathy (Breyer and Tchekneva 2006; Choeiri et al. 2005)
  • Older mutants have difficulty walking and have slow reaction times, normal learning ability and memory
  • Progressive retinal abnormalities begin at about 12 weeks (after hyperglycemia develops)

B6.Cg-Rag1tm1Mom Ins2Akita/J 

004369

  • Spontaneously develops diabetes when young (beta cell deficiency)
  • Severely immunocompromised (no B and T cells)
  • Ideally suited for allogeneic and xenogeneic islet, islet cell, and stem cell transplantation research

LG/J and SM/J 

000675 and 000687

  • Often crossed with each other or to A/J (000646) or NZB/BINJ (000684) to find obesity, diabetes, and cardiovascular disease QTLs (Clee and Attie 2006)
  • Differ in many traits, including obesity, plasma glucose, glucose tolerance, and response to high-fat feeding (Ehrich et al. 2003)
  • When both are fed a high-fat diet, SM mice have higher serum glucose levels (Ehrich et al. 2003)
  • Several QTLs for insulin, glucose, and glucose tolerance identified in the LGXSM RI strains (loci affecting glucose and insulin resistance likely different) (Cheverud et al. 2004a, 2004b)
  • Several SMXA RI strains have different body weights and plasma insulin levels (Anunciado et al. 2000)
  • SMXA-5, develops insulin resistance, increased β-cell mass, and may be a useful diabetes model (Kobayashi et al. 2004, 2006; Anunciado et al. 2000)
  • Analysis of an F2 intercross between SMXA-5 and SM revealed several loci affecting plasma glucose levels, insulin levels, and glucose tolerance. One of these loci, on Chr 2, harbors two A/J-derived alleles that contribute to impaired glucose tolerance (Kobayashi et al. 2004)

NON/ShiLtJ

002423

  • Diet induced obesity when fed a 45 kcal% fat diet
  • Impaired glucose tolerance, and moderate transient hyperglycemia
  • Late developing hyperinsulinemia (20-24 weeks of age)
  • Elevated plasma triglycerides, free fatty acids, leptin and resistin
  • Aging-dependent, mild glomerular nephropathy (Leiter et al. 1998)

NOD/ShiLtJ-Leprdb-5J/LtJ

004939

  • Homozygotes of both sexes develop juvenile onset obesity and type 2 diabetes
  • Hyperphagic by five weeks, both sexes hyperglycemic within one to two weeks of weaning
  • Do not require insulin therapy for long tem survival (39+ weeks)
  • Chronically elevated insulin and leptin levels maintained over periods up to 1 year
  • Islet hypertrophy with beta cell hyperplasia typically not restricted by insulitis, which, when present, is primarily peri-vascular/periductular and not intra-islet
  • About 1/3 of progress to end-stage type 2 diabetes (low body weight and plasma insulin; about 2/3 stay obese (35-45g) and exhibit beta cell hypertrophy/hyperplasia (Lee et al. 2005)
  • Serum lipid levels normal
  • No significant liver or kidney pathology (Lee et al. 2005)
  • Whereas splenic leukocytes from young, hyperglycemic mutants transferred into NOD.Rag1 recipients do not transfer type I diabetes over 13 weeks, wild-type donor cells do; however, widespread insulitis is transferred by Leprdb-5J donors, indicating that their splenocytes contain a less-activated effector population at the time of transfer
  • Reciprocal bone marrow transfers confirm that Leprdb-5J marrow contains diabetogenic stem cells; however, the slower diabetes generated by either wild-type or mutant marrow transferred into irradiated Leprdb-5J recipients indicates that the disturbed metabolic milieu produced by the obesity mutation is the major reason for suppressing the diabetogenic potential of marrow precursors (Lee et al. 2006)
  • May be used to research the interaction between the endocrine and immune system in type 1 diabetes-prone mice, understanding the trophic factors generated to produce robust proliferation of B-cells, and studying the involvement of leptin signaling in cueing the cytopathic function of autoimmune T-effector cells