Phenotypes associated with this allele

• Allele Symbol: Akt1^tm1Nhy
• Allele Name: targeted mutation 1, Nissim Hay
• Allele ID: MGI:2181580
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Akt1^tm1Nhy/Akt1^tm1Nhy	involves: 129/Sv * C57BL/6	MGI:2673732
cx2	Akt1^tm1Nhy/Akt1^tm1Nhy Akt2^tm1Rsg/Akt2^tm1Rsg	involves: 129/Sv * C57BL/6 * DBA/1LacJ	MGI:2673733
cx3	Akt1^tm1Nhy/Akt1^+ Akt2^tm1Rsg/Akt2^tm1Rsg Akt3^tm1Nhy/Akt3^tm1Nhy	involves: 129/Sv * C57BL/6 * DBA/1LacJ	MGI:3848164
cx4	Akt1^tm1Nhy/Akt1^+ Akt2^tm1Rsg/Akt2^tm1Rsg Pten^tm1Ppp/Pten^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/1LacJ	MGI:3848161
cx5	Akt1^tm1Nhy/Akt1^+ Akt2^tm1Rsg/Akt2^tm1Rsg	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/1LacJ	MGI:3848163

Genotype
MGI:2673732

hm1

• Allelic Composition: Akt1^tm1Nhy/Akt1^tm1Nhy
• Genetic Background: involves: 129/Sv * C57BL/6

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

mortality/aging

premature death ( J:71404 )

• life span of irradiated mice shortened more than normal

endocrine/exocrine glands

abnormal thymus morphology ( J:71404 )

• higher levels of apoptosis seen in thymus

• thymocytes more sensitive to gamma-irradiation

abnormal testis morphology ( J:71404 )

♂ • however, male mice are fertile

small seminiferous tubules ( J:71404 )

♂ • disturbed layer of differentiating germ cells and uneven thickness of the germ cell layer at 5 weeks of age

seminiferous tubule degeneration ( J:71404 )

♂

growth/size/body

decreased body weight ( J:71404 )

• body weight at 1 month is 15-20% lower than normal

immune system

abnormal thymus morphology ( J:71404 )

• higher levels of apoptosis seen in thymus

• thymocytes more sensitive to gamma-irradiation

reproductive system

multinucleated giant male germ cells ( J:71404 )

♂

abnormal testis morphology ( J:71404 )

♂ • however, male mice are fertile

small seminiferous tubules ( J:71404 )

♂ • disturbed layer of differentiating germ cells and uneven thickness of the germ cell layer at 5 weeks of age

seminiferous tubule degeneration ( J:71404 )

♂

abnormal spermatogenesis ( J:71404 )

♂

oligozoospermia ( J:71404 )

♂ • mature sperm reduced 2-3 fold

♂ • enlarged spermatids and multinucleated cells present in the lument of the seminiferous tubules by 5 weeks of age as opposed to 6 months normally

♂ • increased levels of apoptosis

hematopoietic system

abnormal thymus morphology ( J:71404 )

• higher levels of apoptosis seen in thymus

• thymocytes more sensitive to gamma-irradiation

cellular

oligozoospermia ( J:71404 )

♂ • mature sperm reduced 2-3 fold

♂ • enlarged spermatids and multinucleated cells present in the lument of the seminiferous tubules by 5 weeks of age as opposed to 6 months normally

♂ • increased levels of apoptosis

multinucleated giant male germ cells ( J:71404 )

♂

increased cellular sensitivity to gamma-irradiation ( J:71404 )

• thymocytes more sensitive to gamma-irradiation

Genotype
MGI:2673733

cx2

• Allelic Composition: Akt1^tm1Nhy/Akt1^tm1Nhy; Akt2^tm1Rsg/Akt2^tm1Rsg
• Genetic Background: involves: 129/Sv * C57BL/6 * DBA/1LacJ

mortality/aging

perinatal lethality ( J:83741 )

growth/size/body

decreased birth weight ( J:83741 )

• weights of newborns at birth are only about 50% normal

decreased fetal weight ( J:83741 )

• weights of E18.5 embryos are only about 50% normal

homeostasis/metabolism

abnormal lipid homeostasis ( J:83741 )

• adipocyte differentiation is retarded or does not occur

muscle

muscle hypoplasia ( J:83741 )

• individual muscle fibers are markedly reduced

• individual muscle cells are approximately 50% smaller than normal

respiratory system

respiratory distress ( J:83741 )

• newborn homozygotes display labored breathing

skeleton

delayed bone ossification ( J:83741 )

• ossification barely detectable at E14.5

• at E18.5 there was still extensive cranial cartillage as well as in the axial skeleton and limbs

integument

underdeveloped hair follicles ( J:83741 )

• most hair follicles do not develop beyond very early stage

decreased hair follicle number ( J:83741 )

thin epidermis stratum spinosum ( J:83741 )

• spinous layer particularly affected by skin thinning

abnormal keratinocyte morphology ( J:83741 )

• reduced proliferation of basal keratinocytes

translucent skin ( J:83741 )

thin skin ( J:83741 )

• all layers of skin thinner but present

Genotype
MGI:3848164

cx3

• Allelic Composition: Akt1^tm1Nhy/Akt1⁺; Akt2^tm1Rsg/Akt2^tm1Rsg; Akt3^tm1Nhy/Akt3^tm1Nhy
• Genetic Background: involves: 129/Sv * C57BL/6 * DBA/1LacJ

homeostasis/metabolism

hyperglycemia ( J:149156 )

Genotype
MGI:3848161

cx4

• Allelic Composition: Akt1^tm1Nhy/Akt1⁺; Akt2^tm1Rsg/Akt2^tm1Rsg; Pten^tm1Ppp/Pten⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/1LacJ

homeostasis/metabolism

increased circulating insulin level ( J:149156 )

• following glucose injection, mice exhibit a greater increase in serum insulin levels compared with similarly treated wild-type mice

impaired glucose tolerance ( J:149156 )

• mice exhibit impaired glucose tolerance that is not as severe as in Akt1^tm1Nhy/Akt1^tm1Nhy Akt2^tm1Rsg/Akt2^tm1Rsg mice

• however, mice exhibit normal glucose serum levels under normal conditions

endocrine/exocrine glands

enlarged pancreatic islets ( J:149156 )

• compared to in Akt2^tm1Rsg homozygotes

Genotype
MGI:3848163

cx5

• Allelic Composition: Akt1^tm1Nhy/Akt1⁺; Akt2^tm1Rsg/Akt2^tm1Rsg
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/1LacJ

homeostasis/metabolism

decreased insulin secretion ( J:149156 )

• the few insulin+ beta cells exhibit reduced insulin production compared to in wild-type mice

• ex-vivo, glucose-stimulated beta-cells produce and secrete less insulin than similarly treated wild-type cells

hyperglycemia ( J:149156 )

• as early as 1 month after birth, mice exhibit a 2- to 3-fold increase in serum glucose level compared with wild-type mice whether fed or fasted

• increased glucose levels cannot be lowered by injection of insulin as in wild-type mice

• however, mice treated with a leptin-expressing adenovirus exhibit normal glucose levels

increased circulating insulin level ( J:149156 )

• mice exhibit increased serum insulin levels compared with wild-type mice that are 3-fold lower than in Akt2^tm1Rsg homozygotes

• however, injection of glucose does not increase serum insulin levels

• however, mice treated with a leptin-expressing adenovirus exhibit normal insulin levels

decreased circulating leptin level ( J:149156 )

impaired glucose tolerance ( J:149156 )

• mice exhibit a diabetic response to glucose challenge

endocrine/exocrine glands

decreased pancreatic beta cell number ( J:149156 )

• fewer insulin+ beta-cells are detected in pancreatic islet cells compared to in wild-type mice or Akt2^tm1Rsg homozygotes

enlarged pancreatic islets ( J:149156 )

• compared to in Akt2^tm1Rsg homozygotes

decreased insulin secretion ( J:149156 )

• the few insulin+ beta cells exhibit reduced insulin production compared to in wild-type mice

• ex-vivo, glucose-stimulated beta-cells produce and secrete less insulin than similarly treated wild-type cells

adipose tissue

decreased white adipose tissue amount ( J:149156 )

decreased percent body fat/body weight ( J:149156 )