Phenotypes associated with this allele

• Allele Symbol: Anxa7^tm1Pll
• Allele Name: targeted mutation 1, Harvey B Pollard
• Allele ID: MGI:2159005
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Anxa7^tm1Pll/Anxa7^tm1Pll	Not Specified	MGI:3588100
ht2	Anxa7^tm1Pll/Anxa7^+	B6.Cg-Anxa7^tm1Pll	MGI:3588102
ht3	Anxa7^tm1Pll/Anxa7^+	Not Specified	MGI:3588101

Genotype
MGI:3588100

hm1

• Allelic Composition: Anxa7^tm1Pll/Anxa7^tm1Pll
• Genetic Background: Not Specified

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:58572 )

• homozygous mutant embryos die at ~E10 due to cardiovascular defects; no viable embryos are obtained at E11

cardiovascular system

abnormal cardiovascular system physiology ( J:58572 )

intraventricular hemorrhage ( J:58572 )

• at E10, 8 of 40 mutant embryos display hemorrhages into the brain vesicles in the absence of other developmental anomalies

• such hemorrhages are composed of both mature maternal erythrocytes and fetal nucleated erythroid precursors

nervous system

intraventricular hemorrhage ( J:58572 )

• at E10, 8 of 40 mutant embryos display hemorrhages into the brain vesicles in the absence of other developmental anomalies

• such hemorrhages are composed of both mature maternal erythrocytes and fetal nucleated erythroid precursors

Genotype
MGI:3588102

ht2

• Allelic Composition: Anxa7^tm1Pll/Anxa7⁺
• Genetic Background: B6.Cg-Anxa7^tm1Pll

Metastatic lymphosarcoma of the thymus in Anxa7^tm1Pll/Anxa7⁺ mice

neoplasm

increased tumor incidence ( J:93685 )

• although tumors occur in both heterozygous males and females, females exhibit a higher propensity for tumor development

• by ~1 year of age, ~23% of heterozygotes have developed visible spontaneous tumors (~1-cm or greater in diameter)

• 42% of heterozygotes with visible tumors exhibit lesions in multiple locations

• among 58 males and 79 females analyzed, 1 primary colon tumor was detected in a male, and 2 primary lung tumors were detected in females; single instances of prostate carcinoma, ovarian carcinoma, and salivary gland tumors were observed

increased hepatocellular carcinoma incidence ( J:93685 )

• both male and female heterozygotes develop hepatocellular carcinomas

increased lymphoma incidence ( J:93685 )

• lymphoid tumors involving thymus and spleen comprise 50% and 76% of visible tumors detected in heterozygous males and females, respectively

• frequent diagnoses include lymphosarcomas of the thymus, both localized and metastatic to the lung or pancreas

reproductive system

reproductive system phenotype ( J:307472 )

♀N • similar numbers of oocytes are produced by homozygous mutant mice compared to controls

abnormal embryo implantation ( J:307472 )

♀ • increased number of implantation sites

abnormal uterine receptivity ( J:307472 )

♀ • increased receptivity

increased litter size ( J:307472 )

♀

liver/biliary system

increased hepatocellular carcinoma incidence ( J:93685 )

• both male and female heterozygotes develop hepatocellular carcinomas

growth/size/body

increased body size ( J:93685 )

• heterozygous males display gigantism in the absence of obesity

increased body weight ( J:93685 )

• in males, increased growth rate continues uninterrupted for at least one year, leading to 40- to 60-g mice (~25% increase in body weight relative to wild-type)

• in addition, a number of internal organs increase in weight proportionately

increased growth rate ( J:93685 )

• after postnatal week 4, heterozygous males show a significantly enhanced growth spurt relative to wild-type males

• in contrast, heterozygous females show normal growth curves as a function of age

cellular

chromosome breakage ( J:93685 )

• spectral karyotyping indicates that hepatocellular carcinomas display chromosomal instability and clonal chromosomal aberrations, with genomic changes on chromosomes 3, 4, 5, 8, 9, 12, 14, and 19

• moreover, gene-expression profiling of tumors indicates down-regulation of several specific tumor suppressor and DNA-repair genes, contributing to the cancer-prone phenotype

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:93685 )

N • the pituitaries of heterozygous males and females appear histologically normal

N • heterozygous males exhibit normal plasma insulin-like growth factor 1 and corticosterone levels

N • in addition, no changes in luteinizing hormone, growth hormone, thyrotropin, prolactin, alpha-melanocyte-stimulating hormone, beta-endorphin, or corticotropin levels are observed

Genotype
MGI:3588101

ht3

• Allelic Composition: Anxa7^tm1Pll/Anxa7⁺
• Genetic Background: Not Specified

Islet hyperplasia in Anxa7^tm1Pll/Anxa7⁺ mice

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:58572 )

• at ~3 months, both female and male heterozygotes show beta cell hypertrophy

• the average diameters of heterozygous beta cells are ~75% greater than those of wild-type beta cells

enlarged pancreatic islets ( J:58572 )

• at ~3 months, heterozygotes display significantly enlarged islets relative to wild-type

pancreatic islet hyperplasia ( J:58572 )

• starting at ~6 weeks, both female and male heterozygotes display islet cell hyperplasia

abnormal pancreatic beta cell physiology ( J:58572 )

• the insulin-containing secretory vesicles in mutant beta cells display an ~2-fold increase in insulin relative to vesicles in wild-type beta cells

decreased insulin secretion ( J:58572 )

• heterozygous mutants show no significant differences in insulin tolerance tests relative to wild-type mice

• isolated heterozygous islets show a significant defect in calcium-dependent insulin secretion, despite an observed 8- to 10-fold increase in the levels of total insulin; impaired insulin secretion is probably caused by altered Ca²⁺ signaling

• glucose metabolism, K_ATP channels, and voltage-gated channels remain functionally intact in mutant beta cells

pancreas inflammation ( J:58572 )

• at ~3 months, heterozygotes exhibit a mild inflammatory invasion of the pancreatic duct

homeostasis/metabolism

decreased insulin secretion ( J:58572 )

• heterozygous mutants show no significant differences in insulin tolerance tests relative to wild-type mice

• isolated heterozygous islets show a significant defect in calcium-dependent insulin secretion, despite an observed 8- to 10-fold increase in the levels of total insulin; impaired insulin secretion is probably caused by altered Ca²⁺ signaling

• glucose metabolism, K_ATP channels, and voltage-gated channels remain functionally intact in mutant beta cells

abnormal ion homeostasis ( J:58572 )

• heterozygotes exhibit Ca²⁺-dependent endocrine secretory defects, suggesting that annexin A7 is involved in Ca²⁺ signaling and/or Ca²⁺ homeostasis

• heterozygotes show altered expression of the inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3] receptor and a resulting failure of Ins(1,4,5)P3-induced Ca²⁺ release from internal stores, which is typically required for insulin secretion from pancreatic islet cells

immune system

pancreas inflammation ( J:58572 )

• at ~3 months, heterozygotes exhibit a mild inflammatory invasion of the pancreatic duct